Search CTL/CD8+ T-Cell Epitope Database

Found 152 matching records:

Displaying record number 1404

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART

Notes

• Administration of triple-drug antiretroviral therapy (IDV, 3TC and ZDV) sometimes showed a transient increase and other times failed to increase CTL responses in patients with advanced HIV disease, but there is a stable population of tetramer stained HIV-specific CD8+ CD45RO+ cells that persist after therapy and long periods of virus being below the level of detection.

References

Rinaldo2000 C. R. Rinaldo, Jr., X. L. Huang, Z. Fan, J. B. Margolick, L. Borowski, A. Hoji, C. Kalinyak, D. K. McMahon, S. A. Riddler, W. H. Hildebrand, R. B. Day, and J. W. Mellors. Anti-human immunodeficiency virus type 1 (HIV-1) CD8(+) T-lymphocyte reactivity during combination antiretroviral therapy in HIV-1-infected patients with advanced immunodeficiency. J. Virol., 74(9):4127-38, May 2000. URL: http://jvi.asm.org/cgi/content/full/74/9/4127. PubMed ID: 10756025. Show all entries for this paper.

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Displaying record number 62553

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(464-472)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Subtype	B
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Patient MHC/HLA	S00085: A*02, A*33, B*57, B*65, C*08, C*18
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	dynamics, chronic infection

Notes

• This report analyzed 29 CTL responses against 23 HIV-1 epitopes in 9 untreated chronically infected "controllers" and identified inverse correlations between epitope variability and CTL clonal stability over time and between epitope variability and CTL clonal breadth.
• Over 17 weeks, the ILKEPVHGV-specific CTL clonal response in individual S00085 demonstrated a 0.91 Sorenson similarity index and a mean breadth of 2.5.
• Based on all HIV-1 subtype B sequences in LANL HIV Sequence Database at time of analysis, ILKEPVHGV had a Simpson diversity index of 0.43.

References

Balamurugan2017 Arumugam Balamurugan, Deon Claiborne, Hwee L. Ng, and Otto O. Yang. HIV-1 Epitope Variability Is Associated with T Cell Receptor Repertoire Instability and Breadth. J. Virol., 91(16), 15 Aug 2017. PubMed ID: 28592539. Show all entries for this paper.

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Displaying record number 54575

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(309-317)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Subtype	B
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	Intracellular cytokine staining, Other
Keywords	rate of progression, escape, mutation acquisition

Notes

• To correlate evolving HIV-1 populations with HLA-A2 restricted immune responses for epitopes in Gag, Pol, Env and Nef, 11 treatment-naive subjects were longitudinally studied. Results show that increased viral load is often associated with broad CTL responses early in infection that persist as an "immunological footprint". Conversely, early, restricted responses may help limit viral load. Phylogenetic and functional evidence of viral escape is seen in Gag, Nef and Pol. Gag and Nef show flanking epitope changes restricted by non-HLA-A2 alleles. As far as modes of viral adaptation, CTL responses were seen to develop both against static viral populations resulting in viral evolution to HLA-A2 as well as against existing mutants resulting in reselection of consensus B-like variants. This study reinforces that CTL immune responses detected are not necessarily beneficial to patients, but may be "footprints" from early effective responses that the virus has since escaped.
• Responses to epitope IV9 were seen in early chronic infection.

References

Karlsson2007 Annika C. Karlsson, Astrid K. N. Iversen, Joan M. Chapman, Tulio de Oliviera, Gerald Spotts, Andrew J. McMichael, Miles P. Davenport, Frederick M. Hecht, and Douglas F. Nixon. Sequential Broadening of CTL Responses in Early HIV-1 Infection Is Associated with Viral Escape. PLoS ONE, 2:e225, 2007. PubMed ID: 17311088. Show all entries for this paper.

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Displaying record number 53091

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT Pol(464-472)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Country	Spain
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay, Proliferation
Keywords	HAART, ART, supervised treatment interruptions (STI)

Notes

• Structured treatment interruption (STI) alone is not able to control viral replication in chronically infected patients, probably due to lack of strong, maintained T-helper cell responses. HIV-1 specific CD8+ T-cell responses were shown to increase significantly until the end of the follow up, but were not correlated with viral load.
• 9/19 patients recognized this epitope.

References

Plana2004 Montserrat Plana, Felipe Garcia, Annette Oxenius, Gabriel M. Ortiz, Anna Lopez, Anna Cruceta, Gabriel Mestre, Emilio Fumero, Catherine Fagard, Maria Antonia Sambeat, Ferran Segura, José M. Miró, Mireia Arnedo, L. Lopalcos, Tomas Pumarola, Bernard Hirschel, Rodney E. Phillips, Douglas F. Nixon, Teresa Gallart, and Jose M. Gatell. Relevance of HIV-1-Specific CD4+ Helper T-Cell Responses During Structured Treatment Interruptions in Patients With CD4+ T-Cell Nadir Above 400/mm3. J. Acquir. Immune Defic. Syndr., 36(3):791-799, 1 Jul 2004. PubMed ID: 15213562. Show all entries for this paper.

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Displaying record number 1768

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(309-317)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Experimental methods
Keywords	rate of progression, acute/early infection

Notes

• The CTL response to optimally defined CTL epitopes restricted by HLA class I A and B alleles in individuals who coexpressed HLA A*02, A*03, and B*07 was studied in eight HIV-1-infected subjects, two with acute infection, five with chronic, and one long-term non-progressor (LTNP)
• 2 to 17 epitopes were recognized in a given individual, A*02-restricted CTL response tended to be narrow and never dominated the response, and 25/27 epitopes were targeted by at least one person.

References

Day2001 C. L. Day, A. K. Shea, M. A. Altfeld, D. P. Olson, S. P. Buchbinder, F. M. Hecht, E. S. Rosenberg, B. D. Walker, and S. A. Kalams. Relative dominance of epitope-specific cytotoxic T-lymphocyte responses in human immunodeficiency virus type 1-infected persons with shared HLA alleles. J. Virol., 75(14):6279-91, Jul 2001. URL: http://jvi.asm.org/cgi/content/full/75/14/6279. PubMed ID: 11413294. Show all entries for this paper.

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Displaying record number 54794

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(309-317)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Experimental methods	CTL suppression of replication
Keywords	class I down-regulation by Nef

Notes

• The impact of Nef on antiviral activity was studied. CTL-targeting epitopes were susceptible to the effects of Nef, both in late (Gag, RT, Env) and in early proteins (Rev, Nef), although to a lesser degree in early proteins. HLA-C-restricted CTLs (unlike HLA-A and HLA-B) were unaffected by Nef both in early (Nef) and late (Env) proteins.
• Late protein RT epitope ILKEPVHGV-recognizing CTLs were affected by Nef.

References

Adnan2006 Sama Adnan, Arumugam Balamurugan, Alicja Trocha, Michael S. Bennett, Hwee L. Ng, Ayub Ali, Christian Brander, and Otto O. Yang. Nef Interference with HIV-1-Specific CTL Antiviral Activity Is Epitope Specific. Blood, 108(10):3414-3419, 15 Nov 2006. PubMed ID: 16882705. Show all entries for this paper.

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Displaying record number 62244

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(464-472)
Epitope	ILKEPVHGV	Epitope Alignment
		Show epitope variants
Epitope Name	Pol-IV9
Subtype	C
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Patient MHC/HLA	021-C: A*02:05, A*29:02, B*42:01, B*44:03, C*02:10, C*17:01; 021-M: A*02:05, A*33:01, B*42:01, B*44:03, C*02:10, C*17:01
Country	South Africa, United Kingdom
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	dynamics, responses in children, mother-to-infant transmission, rate of progression, escape

Notes

• 11 perinatally infected pediatric slow progressors (PSPs) were followed longitudinally for a decade from birth to examine CTL responses to circulating and autologous HIV. It was found by ultra-deep sequencing that though, like adults, children develop variants early in infection; unlike adults, pediatric anti-variant CTL are generated.
• EliSpot was used to determine that non-Gag/Pol-specific responses (i.e. Env or Nef responses) are higher within the first weeks of infection for pediatric viremic non-controllers (VNCs) just as seen previously in adult VNCs and vice versa in pediatric VCs (PSPs). Therefore non-Gag/Pol-specific CTL responses are confirmed to be linked to higher VL and progression to disease.
• In pediatric A*02⁺ VNC, 021-C, A*02-restricted IV9 was transmitted, potentially with a mutation, from the A*02⁺ mother (Patient Rec. #4461). Additional variants were observed over the sampling time points but none are known to be escape variants.

References

Leitman2017 Ellen M. Leitman, Christina F. Thobakgale, Emily Adland, M. Azim Ansari, Jayna Raghwani, Andrew J. Prendergast, Gareth Tudor-Williams, Photini Kiepiela, Joris Hemelaar, Jacqui Brener, Ming-Han Tsai, Masahiko Mori, Lynn Riddell, Graz Luzzi, Pieter Jooste, Thumbi Ndung'u, Bruce D. Walker, Oliver G. Pybus, Paul Kellam, Vivek Naranbhai, Philippa C. Matthews, Astrid Gall, and Philip J. R. Goulder. Role of HIV-Specific CD8+ T Cells in Pediatric HIV Cure Strategies after Widespread Early Viral Escape. J. Exp. Med., 214(11):3239-3261, 6 Nov 2017. PubMed ID: 28983013. Show all entries for this paper.

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Displaying record number 62496

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(464-472)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Species (MHC/HLA)	human(A*02)
Immunogen	in vitro stimulation or selection, engineered
Experimental methods	CTL suppression of replication, Chromium-release assay, Peptide titration
Keywords	assay or method development, variant cross-reactivity, characterizing CD8+ T cells, neutralization by CTL

Notes

• Low-avidity cross-reactivities against HLA-matched HIV epitopes were commonly found in HIV-specific CTL clones but did not contribute to viral suppression activity. In A*02- and B*57-restricted CTL clones, only primary epitope specificities were identified by a viral suppression assay but cross-reactivities were also identified by standard chromium release and CTL IFNγ EliSpot assays, which often use supraphysiological peptide concentrations.
• ILKEPVHGV-specific CTL clone 68A62 cross-recognized 2 of 28 A*02-restricted epitopes (TLNAWVKVV and LVGPTPVNI) but with substantially lower functional avidity and demonstrated viral suppression when co-cultured with a T-cell line infected with NL4-3 HIV.

References

Balamurugan2018 Arumugam Balamurugan, Hwee L. Ng, and Otto O. Yang. Cross-Reactivity against Multiple HIV-1 Epitopes Is Characteristic of HIV-1-Specific Cytotoxic T Lymphocyte Clones. J. Virol., 92(16), 15 Aug 2018. PubMed ID: 29899094. Show all entries for this paper.

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Displaying record number 56712

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(309-317 HIV-1 NL4-3.1)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Subtype	B
Species (MHC/HLA)	human(A*02)
Immunogen	virus
Experimental methods	CTL suppression of replication
Keywords

Notes

• To assess whether a mutation in an HIV-1 tyrosine-based sorting motif (Y712xxφ) in the membrane-proximal cytoplasmic domain of gp41 affects viral susceptibility to CTLs, point mutations were made in NL4-3.1 at EnvY712I, EnvY712S or EnvΔGY. EnvY712I and EnvY712S did not affect viral growth kinetics, but EnvΔGY virus was replication incompetent.
• An in vitro virus suppression assay using HIV-1 specific CTL clone S31-IV9-10.11T that recognizes HLA A*02-restricted epitope ILKEPVHGV in RT showed similar suppression of the mutant and wild-type viruses. Thus the mechanism of attenuation of infection of these mutants is either not mediated by CTLs or indirectly increases antiviral CTL activity.

References

Cruz2009 Justin De La Cruz, Ayub Ali, Hwee L Ng, and Otto O Yang. Disruption of an env Tyrosine-Dependent Sorting Signal Does Not Affect Susceptibility of HIV-1 to Cytotoxic T Lymphocytes. AIDS, 23(11):1449-1451, 17 Jul 2009. PubMed ID: 19564727. Show all entries for this paper.

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Displaying record number 499

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART

Notes

• The single cell ELISPOT assay was optimized and highly specific, and found to work well even after the primary cells had been frozen and thawed.
• Increases in gamma interferon producing cells were observed in response to anti-retroviral therapy using single cell IFN-gamma-production ELISPOT.

References

Huang2000 X. L. Huang, Z. Fan, C. Kalinyak, J. W. Mellors, and C. R. Rinaldo. CD8+ T Cell Gamma Interferon Production Specific for Human Immunodeficiency Virus Type 1 (HIV-1) in HIV-1-Infected Subjects. Clin. Diagn. Lab. Immunol., 7:279-287, 2000. PubMed ID: 10702505. Show all entries for this paper.

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Displaying record number 1982

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	Pol-IV9; RT-IV9
Subtype	B
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	HAART, ART

Notes

• Among HIV+ individuals who carried HLA A*02, 9/29 (31%) recognized this epitope.

References

Sabbaj2003 Steffanie Sabbaj, Anju Bansal, G. Douglas Ritter, Christopher Perkins, Bradley H. Edwards, Ethan Gough, Jianming Tang, James J. Szinger, Bette Korber, Craig M. Wilson, Richard A. Kaslow, Mark J. Mulligan, and Paul A. Goepfert. Cross-Reactive CD8+ T Cell Epitopes Identified in US Adolescent Minorities. J. Acquir. Immune Defic. Syndr., 33(4):426-438, 1 Aug 2003. PubMed ID: 12869831. Show all entries for this paper.

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Displaying record number 57288

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Subtype	B
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Country	Barbados, Haiti, Jamaica
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	mother-to-infant transmission, elite controllers

Notes

• To dissect whether the protective effect of HLA-B*57 in HIV-1 infection is due to CTL that recognize HLA-B*57-restricted epitopes or by the presence of viral-fitness attenuating mutations in such B*57 epitopes, 13 mother-infant pairs were studied. The B57 advantage is primarily through the maintenance of a fitness-attenuating mutation in p24-Gag, T242N in epitope TW10 (TSTLQEQIGW).
• Regardless of parental inheritance, HLA-B57 controls VL even in infancy and even when escape mutations from B*57 positive mothers are transmitted. Mutations in p24-Gag are predominant in mismatched-HLA subject pairs and arise after vertical transmission, impacting viral fitness.
• Non-B57-epitope IV9-RT, ILKEPVHGV restricted by A*02, was recognized by an infant with maternally-inherited B57.

References

Schneidewind2009 Arne Schneidewind, Yanhua Tang, Mark A. Brockman, Elizabeth G. Ryland, Jacqueline Dunkley-Thompson, Julianne C. Steel-Duncan, M. Anne St. John, Joseph A. Conrad, Spyros A. Kalams, Francine Noel, Todd M. Allen, Celia D. Christie, and Margaret E. Feeney. Maternal Transmission of Human Immunodeficiency Virus Escape Mutations Subverts HLA-B57 Immunodominance but Facilitates Viral Control in the Haploidentical Infant. J. Virol., 83(17):8616-8627, Sep 2009. PubMed ID: 19515764. Show all entries for this paper.

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Displaying record number 55152

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Protease-RT(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02)
Immunogen	in vitro stimulation or selection, HIV-1 infection
Experimental methods	Other
Keywords	kinetics

Notes

• Experimental and mathematical models were used to estimate the number of HIV-infected cells that can be killed by CD8+ T-cells. On average, CTLs can kill from 0.7 to 3.0 cells/day.
• CTL clone 68A62 recognizes epitope ILKEPVHGV and was used to study the inhibition of HIV-1 replication in acutely infected cells in vitro.

References

Wick2005 W. David Wick, Otto O. Yang, Lawrence Corey, and Steven G. Self. How Many Human Immunodeficiency Virus Type 1-Infected Target Cells Can a Cytotoxic T-Lymphocyte Kill? J. Virol., 79(21):13579-13586, Nov 2005. PubMed ID: 16227278. Show all entries for this paper.

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Displaying record number 57396

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(464-473)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Subtype	B
Species (MHC/HLA)	human(A*02)
Immunogen	in vitro stimulation or selection, HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	TCR usage, assay or method development, chronic infection

Notes

• By using a modified spectratyping (immunoscoping) method, epitope-specific TCR breadth and sequences were quantitated rapidly. Overall magnitude of HIV-1 specific CTL responses to chronic infection were limited by the clonal breadth of TCR generated against HIV-1 epitopes tested in 12 patients with chronic, untreated infection.
• CTL response specific to epitope IV9 was studied, TCR usage was BV07, BV12, BV28 and BV20 in patient 00031.

References

Balamurugan2010 Arumugam Balamurugan, Hwee L. Ng, and Otto O. Yang. Rapid T Cell Receptor Delineation Reveals Clonal Expansion Limitation of the Magnitude of the HIV-1-Specific CD8+ T Cell Response. J. Immunol., 185(10):5935-5942, 15 Nov 2010. PubMed ID: 20944001. Show all entries for this paper.

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Displaying record number 59118

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	HIV-1
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Country	Netherlands
Experimental methods	CD8 T-cell Elispot - IFNγ, Tetramer binding
Keywords	binding affinity, elite controllers

Notes

• The mechanisms of protection of HLA-B*57 and -B*27 restricted CTL responses were compared. Differences include: (1) HLA-B*57 but not -B*27 responses are exceptionally high affinity (2) HLA-B*57 responses seem to downregulate CTL responses through other HLA molecules, but -B*27-restricted responses upregulate responses by other host HLA (3) both HLA are protective at distinct times of infection, i.e., B*57 acts early after infection before CD4+ T-cell counts drop below 200 cells/ml, while B*27 effects are seen during chronic infection, after CD4+ T cells have dropped below the 200 cells/ml point. Similarities were that both HLAs' responses were (1) broad (2) not well maintained through disease progression (3) of comparable breadth and magnitude during chronic infection.
• 29 HLA-B*57 and 19 HLA-B*27-restricted peptides were tested in a cohort of 18 B-27+ and 6 B-57+ individuals (see supplement for list of peptides).
• Tetramer decay assays show that the half life for HLA-B*57-peptide complexed with TCR is significantly stronger than that of peptide-HLA-A*02-TCR; however, pHLA-B*27-TCR is not. In patient 8, B*27-KY9(KRKGGIGGY), had a mean fluorescent intensity of t_1/2=257 min while A*02-IV9(ILKEPVHGV)'s was 244 min.

References

Schellens2014 Ingrid M. M. Schellens, Hilde B. Spits, Marjon Navis, Geertje H. A. Westerlaken, Nening M. Nanlohy, Luc E. Coffeng, Neeltje Kootstra, Frank Miedema, Hanneke Schuitemaker, José A. M. Borghans, and Debbie van Baarle. Differential Characteristics of Cytotoxic T Lymphocytes Restricted by the Protective HLA Alleles B*27 and B*57 in HIV-1 Infection. J. Acquir. Immune Defic. Syndr., 67(3):236-245, 1 Nov 2014. PubMed ID: 25171732. Show all entries for this paper.

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Displaying record number 59811

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT Pol(309-317)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope, chronic infection

Notes

• Correlation between HLA class I and spontaneous control of HIV-1 was significant for 7-8 epitopes when 341 chronic, HIV-infected subjects, divided into controllers and non-controllers, were tested for EliSpot responses to 257 optimally defined epitopes. 21 epitopes were associated with viral progression. Protective epitopes tend to cluster in regions of critical stability for the protein, therefore constraining escape.
• ILKEPVHGV had a significantly positive association with HLA A*02; it was recognized by 45/142 A*02-positive subjects and 3/199 A*02-negative subjects.
• IKLEPVHGV was significantly nonprotective, associated with HIV chronic disease progression when restricted by HLA-A*02 in a cohort of 245 controllers and 96 progressors.

References

Pereyra2014 Florencia Pereyra, David Heckerman, Jonathan M. Carlson, Carl Kadie, Damien Z. Soghoian, Daniel Karel, Ariel Goldenthal, Oliver B. Davis, Charles E. DeZiel, Tienho Lin, Jian Peng, Alicja Piechocka, Mary Carrington, and Bruce D. Walker. HIV Control Is Mediated in Part by CD8+ T-Cell Targeting of Specific Epitopes. J. Virol., 88(22):12937-12948, Nov 2014. PubMed ID: 25165115. Show all entries for this paper.

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Displaying record number 53862

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	POL
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Country	France
Experimental methods	Cytokine production, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining, Tetramer binding
Keywords	responses in children, characterizing CD8+ T cells

Notes

• Only a fraction of HIV-1-specific CD8 T-cells detected in the PBMC of 17 infected children (ages 2-18) were able to produce cytokines (IFN-gamma, TNF-alpha) or chemokines (CCL4, CCL5) after stimulation with the cognate peptide. A negative correlation was found between the plasma viral load and the precentage of CD8+ Gag-specific T-cells secreting IFN-gamma. Tetramers used in this study were SLYNTVATL-HLA-A*02 and ILKEPVHGV-HLA-A*02.

References

Scott-Algara2005a Daniel Scott-Algara, Florence Buseyne, Françoise Porrot, Beatrice Corre, Nassima Bellal, Christine Rouzioux, Stephane Blanche, and Yves Riviere. Not All Tetramer Binding CD8+ T Cells Can Produce Cytokines and Chemokines Involved in the Effector Functions of Virus-Specific CD8+ T Lymphocytes in HIV-1 Infected Children. J. Clin. Immunol., 25(1):57-67, Jan 2005. PubMed ID: 15742158. Show all entries for this paper.

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Displaying record number 500

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02)
Immunogen	vaccine
Experimental methods
Keywords

Vaccine Details

Vaccine type	vaccinia

Notes

• A polyepitope vaccine was generated in a vaccinia construct that contiguously encoded seven epitopes, all presented by HLA-A*02.
• HHD mice have a transgene of HLA-A*02 linked to the transmembrane and cytotoxic domains of H-2D^d -- this transgene is the only MHC molecule expressed in the mice.
• CTL responses to Gag (77-85) SLYNTVATL, Pol (476-484) ILKEPVHGV, gp120 (120-128) KLTPLCVTL, and Nef (190-198) AFHHVAREL were observed in HIV polytope HHD-vaccinated mice, and these responses were enhanced with vaccinia boost.
• No CTL immune responses were generated against HLA-A*02-restricted HIV epitopes Nef 157-166 (PLTFGWCYKL), Pol 346-354 (VIYQYMDDL), and Nef 180-189 (VLEWRFDSRL)
• Sixteen HLA-A*02+ patients were tested for their ability to make CTL responses by peptide restimulation in culture with the epitopes selected for inclusion in the polytope -- one individual recognized all seven of these epitopes; 7 patients had CTL cultures able to recognize at least one of the epitopes, and 6 of those 7 recognized more than one epitope, but they were not able to test all peptides for all patients; many patients only had three peptides tested.
• ILKEPVHGV was recognized by 2 of the patients.

References

Woodberry1999 T. Woodberry, J. Gardner, L. Mateo, D. Eisen, J. Medveczky, I. A. Ramshaw, S. A. Thomson, R. A. Ffrench, S. L. Elliott, H. Firat, F. A. Lemonnier, and A. Suhrbier. Immunogenicity of a Human Immunodeficiency Virus (HIV) Polytope Vaccine. J. Virol., 73:5320-5325, 1999. PubMed ID: 10364278. Show all entries for this paper.

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Displaying record number 58303

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(464-)
Epitope	ILKEPVHGV	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Country	Canada
Experimental methods	Other
Keywords	characterizing CD8+ T cells, elite controllers

Notes

• Dual color EliSpot testing for IL-2 and IFN-γ was used to determine whether CTL restricted by MHC Class I alleles associated with slow progression to disease, viz. B*57 and B*27, had a more poly-functional profile than other CD8+ cells in a treatment-naive cohort from Montreal. B*57/B*27-restricted CTL producing IL-2 or IFN-γ or IL-2/IFN-γ, were similar in both slow progressors (SP) and progressors. Other non-protective MHC-I-restricted CTL producing both IL-2/IFN-γ, were greater in number in SP than progressors.
• Within SP, peptides restricted by both protective and non-protective MHC-I alleles elicited CTL with the same functional profile. For progressors, peptides and epitopes restricted by protective B*57/B*27 alleles stimulated a higher proportion of dual-(IL-2/IFN-γ)secreting CTL.
• HLA-A*02-restricted Pol optimal epitope ILKEPVHGV was tested in a dual color EliSpot and found to elicit CTL that could produce IL-2 and/or IFN-γ.

References

Peretz2011 Yoav Peretz, Olivia Marra, Réjean Thomas, Danielle Legault, Pierre Côté, Mohamed-Rachid Boulassel, Danielle Rouleau, Jean-Pierre Routy, Rafick-Pierre Sékaly, Christos M Tsoukas, Cécile Tremblay, and Nicole F. Bernard. Relative Contribution of HIV-Specific Functional Lymphocyte Subsets Restricted by Protective and Non-Protective HLA Alleles. Viral Immunol, 24(3):189-198, Jun 2011. PubMed ID: 21668360. Show all entries for this paper.

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Displaying record number 58379

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(309-317)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Subtype	B
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Country	France, Germany
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	drug resistance

Notes

• Epitope YV9 of RT was chosen to study the response of patients with virological failure whose epitope/s contain drug resistance mutations. The resistance mutation due to drugs lamivudine (3TC) and emtricitabine (FTC) in YV9 is M184V,YQYvDDLYV (YV9V). YV9 carries a fitness cost that makes it unlikely to find in ART-naive patients. Responses to YV9 were compared to epitope VL9, VIYQYMDDL, whose variant, YIYQYvDDL (VL9V), is not a drug resistant mutation.
• Wild-types and mutants YV9 and VL9 (as well as HLA-A2-restricted epitopes in Gag and RT) were tested for frequency and magnitude of EliSpot response in subjects who were ART-naive or not. CTL response to YV9 was common, though not to VL9, in HLA-A2+ subjects. Responses to YV9 correlated with VL, and YV9 polymorphism upstream of the epitope at D177E.
• 8/19 ART-naive, 5/15 3TC subjects responded to ILKEPVHGV, IV9, with CTL. These responses were equivalent to responses of the epitope under study, YV9, in frequency and magnitude.

References

Pacheco2011 Yovana Pacheco, Clotilde Allavena, Yannick Guilloux, Sandra M. Mueller-Schmucker, Angela G. Hueckelhoven, Elisabeth André-Garnier, François Cleon, Virginie Ferré, Audrey Rodallec, Eric Billaud, Thomas Harrer, François Raffi, and Dorian McIlroy. The Immune Response to the RT181-189 Epitope in HIV-1-Infected Patients Is Associated with Viral Sequence Polymorphism Flanking the Epitope. J. Clin. Immunol., 31(4):681-689, Aug 2011. PubMed ID: 21491096. Show all entries for this paper.

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Displaying record number 1581

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART, immunodominance

Notes

• This study examined with CTL response in HLA A*02+ children by tetramer staining for HLA-A2 immunodominant epitopes SLYNTVATL and ILKEPVHGV.
• 71% of the 28 HIV-1 infected HLA-A*02 positive children recognized both epitopes, with cells from 26 children stained positive by the gag tetramer (SLYNTVATL) and 21 children by the pol tetramer (ILKEPVHGV)
• There were no differences observed in children that had therapy versus those that did not.
• Tetramer-binding cells were memory activated CD28-, CD45RO+, CD45RA- HLADR+, CD69-, CD8+ T-cells.

References

ScottAlgara2001 D. Scott-Algara, F. Buseyne, S. Blanche, C. Rouzioux, C. Jouanne, F. Romagne, and Y. Riviere. Frequency and phenotyping of human immunodeficiency virus (HIV)-specific CD8+ T cells in HIV-infected children, using major histocompatibility complex class I peptide tetramers. J. Infect. Dis., 183(11):1565-73, 1 Jun 2001. PubMed ID: 11343205. Show all entries for this paper.

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Displaying record number 58758

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(446-472)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	Pol-IV9
Subtype	B
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Country	Australia, Canada, United States
Experimental methods	Chromium-release assay
Keywords	class I down-regulation by Nef

Notes

• Factors impacting Nef-mediated immune evasion were studied using 17 epitopes and the kinetics of infected cell clearance. Recognition and clearance of infected presenting cells by Gag-specific CTL is dependent upon the specific epitope it presents as well as virus inoculum (multiplicity of infection, moi), but not on the particular restricting HLA or on any kinetic advantage for early expressed proteins like Rev, Tat and Nef.
• HLA-A*02-restricted Pol-IV9-specific CTL were used in this study.

References

Chen2012 Diana Y. Chen, Arumugam Balamurugan, Hwee L. Ng, William G. Cumberland, and Otto O. Yang. Epitope Targeting and Viral Inoculum Are Determinants of Nef-Mediated Immune Evasion of HIV-1 from Cytotoxic T Lymphocytes. Blood, 120(1):100-111, 5 Jul 2012. PubMed ID: 22613796. Show all entries for this paper.

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Displaying record number 1489

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol( LAI)
Epitope	ILKEPVHGV	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*02:01)
Immunogen	in vitro stimulation or selection
Experimental methods
Keywords	dendritic cells

Notes

• Recombinant canarypox virus vector containing HIV-1 sequences, upon infection of mature dendritic cells, can trigger specific lysis through in vitro by T-cells from HIV-1 infected individuals at levels comparable to the response seen to HIV carried in vaccinia vectors.
• Recombinant canarypox virus vector containing HIV-1 sequences can also stimulate HIV-specific CD4+ helper T-cell responses.

References

Engelmayer2001 J. Engelmayer, M. Larsson, A. Lee, M. Lee, W. I. Cox, R. M. Steinman, and N. Bhardwaj. Mature dendritic cells infected with canarypox virus elicit strong anti-human immunodeficiency virus CD8+ and CD4+ T-cell responses from chronically infected individuals. J. Virol., 75(5):2142-53, Mar 2001. URL: http://jvi.asm.org/cgi/content/full/75/5/2142. PubMed ID: 11160718. Show all entries for this paper.

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Displaying record number 55363

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Species (MHC/HLA)	human(A*02:01)
Immunogen	in vitro stimulation or selection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, HLA binding
Keywords	binding affinity, immunodominance, dendritic cells

Notes

• CTL responses to the rarely recognized, subdominant HLA-A2-restricted Gag p24 epitope TLNAWKVV (TV9) were studied since its functional sensitivity and viral suppression is relatively high compared to other, dominant HLA-A2-restricted HIV-1 epitopes. Subdominant CTL responses to TV9 were not related to immunogenicity, availability of cognate TCR repertoires or HLA-epitope binding avidity.
• HLA-A2 restricted epitope IV9 of Pol was able to stimulate a clone of TV9-specific CTLs that had been pre-primed by Gag+Pol transduced DCs, to produce IFN-gamma.

References

Schaubert2007 Keri L. Schaubert, David A. Price, Nicole Frahm, Jinzhu Li, Hwee L. Ng, Aviva Joseph, Elyse Paul, Biswanath Majumder, Velpandi Ayyavoo, Emma Gostick, Sharon Adams, Francesco M. Marincola, Andrew K. Sewell, Marcus Altfeld, Jason M. Brenchley, Daniel C. Douek, Otto O. Yang, Christian Brander, Harris Goldstein, and June Kan-Mitchell. Availability of a Diversely Avid CD8+ T Cell Repertoire Specific for the Subdominant HLA-A2-Restricted HIV-1 Gag p24(19-27) Epitope. J. Immunol., 178(12):7756-7766, 15 Jun 2007. PubMed ID: 17548613. Show all entries for this paper.

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Displaying record number 1518

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

• In a study including many long-term non-progressors, no correlation between plasma virus levels and number of HIV-specific CD8+ T-cells was found.
• High frequencies of circulating CD8+ T-cells were HIV-1 specific, and the majority of these responses were to gag-pol gene products.
• 4/21 subjects were HLA-(A*0201), and of these only 2 subjects (patient 3 and 19) tested positive to this epitope.

References

GeaBanacloche2000 J. C. Gea-Banacloche, S. A. Migueles, L. Martino, W. L. Shupert, A. C. McNeil, M. S. Sabbaghian, L. Ehler, C. Prussin, R. Stevens, L. Lambert, J. Altman, C. W. Hallahan, J. C. de Quiros, and M. Connors. Maintenance of large numbers of virus-specific CD8+ T cells in HIV-infected progressors and long-term nonprogressors. J. Immunol., 165(2):1082-92, 15 Jul 2000. URL: http://www.jimmunol.org/v165n2/1082/1082-abs-frame.html. PubMed ID: 10878387. Show all entries for this paper.

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Displaying record number 522

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	023: A*02, A*03, B*07, B*51
Experimental methods
Keywords	review, escape

Notes

• HLA-identical sibling hemophiliac brothers were both infected with the same batch of factor VIII.
• One, Patient 003, had a response to gag A*02 epitope SLYNTVATL, the other, Patient 023, to pol A*02 epitope ILKEPVHGV. They were tested 6-8 years after infection.
• Viral sequencing from the twin that had no response to SLYNTVATL indicated his virus had the substituted form SLHNAVAVL.
• 71% of an additional set of 22 HIV-1 infected HLA-A*0201 positive donors preferentially responded to gag SLYNTVATL.
• Those individuals with a pol ILKEPVHGV response tended to have mutations in or around SLYNTVATL.
• This entry, Goulder1997e, is a review of immune escape that summarizes this study.

References

Goulder1997 P. J. Goulder, A. K. Sewell, D. G. Lalloo, D. A. Price, J. A. Whelan, J. Evans, G. P. Taylor, G. Luzzi, P. Giangrande, R. E. Phillips, and A. J. McMichael. Patterns of Immunodominance in HIV-1-Specific Cytotoxic T Lymphocyte Responses in Two Human Histocompatibility Leukocyte Antigens (HLA)-Identical Siblings with HLA-A*0201 Are Influenced by Epitope Mutation. J. Exp. Med., 8:1423-1433, 1997. Primary human immunodeficiency virus (HIV) infection is controlled principally by HIV-specific cytotoxic T lymphocytes (CTL) to a steady- state level of virus load, which strongly influences the ultimate rate of progression to disease. Epitope selection by CTL may be an important determinant of the degree of immune control over the virus. This report describes the CTL responses of two HLA-identical hemophiliac brothers who were exposed to identical batches of Factor VIII and became seropositive within 10 wk of one another. Both have HLA-A*0201. The CTL responses of the two siblings were very dissimilar, one donor making strong responses to two epitopes within p17 Gag (HLA-A*0201-restricted SLYNTVATL and HLA-A3-restricted RLRPGGKKK). The sibling responded to neither epitope, but made strong responses to two epitopes presented by HLA-B7. This was not the result of differences in presentation of the epitopes. However, mutations in both immunodominant epitopes of the p17 Gag responder were seen in proviral sequences of the nonresponder. We then documented the CTL responses to two HLA-A*0201-restricted epitopes, in Gag (SLYNTVATL) and Pol (ILKEPVHGV) in 22 other HIV-infected donors with HLA-A*0201. The majority (71\%) generated responses to the Gag epitope. In the 29\% of donors failing to respond to the Gag epitope in standard assays, there was evidence of low frequency memory CTL responses using peptide stimulation of PBMC, and most of these donors also showed mutations in or around the Gag epitope. PubMed ID: 9126923. Show all entries for this paper.

Goulder1997e P. Goulder, D. Price, M. Nowak, S. Rowland-Jones, R. Phillips, and A. McMichael. Co-Evolution of Human Immunodeficiency Virus and Cytotoxic T-Lymphocyte Responses. Immunol. Rev., 159:17-29, 1997. PubMed ID: 9416500. Show all entries for this paper.

Menendez-Arias1998 L. Menendez-Arias, A. Mas, and E. Domingo. Cytotoxic T-Lymphocyte Responses to HIV-1 Reverse Transcriptase. Viral Immunol., 11:167-181, 1998. PubMed ID: 10189185. Show all entries for this paper.

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Displaying record number 55764

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol
Epitope	ILKEPVHGV	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Country	Canada, United States
Experimental methods	Intracellular cytokine staining, Other, Proliferation, Tetramer binding
Keywords	characterizing CD8+ T cells

Notes

• Tim-3+ T cells form a novel population of dysfunctional CTLs in chronic progressors of HIV infection. Tim-3 surface levels correlate positively with viral load and CD38 expression, but correlates inversely with CD4 T-cell counts.
• Tim-3 expressing CTLs have impaired cytokine production and proliferation in response to antigen, which is restored by blocking Tim-3 signaling pathways.
• Tim-3 expressing CTLs are a distinct population from PD-1 expressing CTLs.
• CTLs specific for HLA-A*0201 restricted Pol epitope ILKEPVHGV were used to follow immune response.

References

Jones2008 R. Brad Jones, Lishomwa C. Ndhlovu, Jason D. Barbour, Prameet M. Sheth, Aashish R. Jha, Brian R. Long, Jessica C. Wong, Malathy Satkunarajah, Marc Schweneker, Joan M. Chapman, Gabor Gyenes, Bahareh Vali, Martin D. Hyrcza, Feng Yun Yue, Colin Kovacs, Aref Sassi, Mona Loutfy, Roberta Halpenny, Desmond Persad, Gerald Spotts, Frederick M. Hecht, Tae-Wook Chun, Joseph M. McCune, Rupert Kaul, James M. Rini, Douglas F. Nixon, and Mario A. Ostrowski. Tim-3 Expression Defines a Novel Population of Dysfunctional T Cells with Highly Elevated Frequencies in Progressive HIV-1 Infection. J. Exp. Med., 205(12):2763-2779, 24 Nov 2008. PubMed ID: 19001139. Show all entries for this paper.

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Displaying record number 1640

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART, rate of progression

Notes

• The CTL effector levels (CTLe) were compared in long term non-progressors (LTNP) with low viral load and in patients whose virus was well-suppressed by therapy, using a tetramer assay.
• LTNPs have high memory CTLe numbers and low viral load, while HAART patients had low CTLe numbers and low viral load.

References

Jin2000a X. Jin, G. Ogg, S. Bonhoeffer, J. Safrit, M. Vesanen, D. Bauer, D. Chen, Y. Cao, M. A. Demoitie, L. Zhang, M. Markowitz, D. Nixon, A. McMichael, and D. D. Ho. An antigenic threshold for maintaining human immunodeficiency virus type 1-specific cytotoxic T lymphocytes. Mol Med, 6(9):803-9, Sep 2000. PubMed ID: 11071274. Show all entries for this paper.

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Displaying record number 1701

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

• Combined tetramer and intracellular cytokine staining was used to study the function of circulating CD8+ T cells specific for HIV and CMV.
• HIV-specific CD8+ T cells expressed lower levels of perforin than CMV-specific CD8+ T cells from the same donor, and this was associated with persistent CD27 expression on HIV-specific cells, suggesting impaired maturation.
• In most donors, between 50% and 95% of the activated virus-specific CD8+ T cells produced IFN-γ and MIP-1β with a distinct subset that failed to produce TNF-α

References

Appay2000 V. Appay, D. F. Nixon, S. M. Donahoe, G. M. Gillespie, T. Dong, A. King, G. S. Ogg, H. M. Spiegel, C. Conlon, C. A. Spina, D. V. Havlir, D. D. Richman, A. Waters, P. Easterbrook, A. J. McMichael, and S. L. Rowland-Jones. HIV-specific CD8(+) T cells produce antiviral cytokines but are impaired in cytolytic function. J. Exp. Med., 192(1):63-75, 3 Jul 2000. URL: http://www.jem.org/cgi/content/full/192/1/63. PubMed ID: 10880527. Show all entries for this paper.

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Displaying record number 56142

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Species (MHC/HLA)	human(A*02:01)
Immunogen	virus
Experimental methods
Keywords	immunotherapy, TCR usage

Notes

• To circumvent failed adoptive transfer of ex-vivo expanded autologous HIV-1-specific CTLs, the authors use autologous peripheral CTLs with redirected antigen specificities instead. CTLs were transduced with lentiviral vectors encoding TCR-alpha and TCR-beta specific for a control, immunodominant Gag epitope, SL9. Potent and specific in vitro and in vivo activity of the transduced CTLs against SL9-presenting cells was seen.
• IV9 epitope was used as a control to show that while IFN-gamma production was induced by the addition of SL9 to transduced CTLs, no cytokine production was induced by addition of IV9 peptide.

References

Joseph2008 Aviva Joseph, Jian Hua Zheng, Antonia Follenzi, Teresa Dilorenzo, Kaori Sango, Jaime Hyman, Ken Chen, Alicja Piechocka-Trocha, Christian Brander, Erik Hooijberg, Dario A. Vignali, Bruce D. Walker, and Harris Goldstein. Lentiviral Vectors Encoding Human Immunodeficiency Virus Type 1 (HIV-1)-Specific T-Cell Receptor Genes Efficiently Convert Peripheral Blood CD8 T Lymphocytes into Cytotoxic T Lymphocytes with Potent In Vitro and In Vivo HIV-1-Specific Inhibitory Activity. J. Virol., 82(6):3078-3089, Mar 2008. PubMed ID: 18184707. Show all entries for this paper.

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Displaying record number 56185

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(498-)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	vaccine
Country	Botswana, United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay
Keywords	vaccine antigen design

Vaccine Details

Vaccine type	DNA, polyepitope
Vaccine strain	multiple epitope immunogen

Notes

• This is a trial of a multi-epitope DNA vaccine that included 21 CTL epitopes, which are conserved among clades A,B,C,D and CRFs and are supertype binding peptides of A1, A3 and B7 supertypes. Participants were from US and Botswana.
• The vaccine was safe and well-tolerated, but the rate of CTL induction was low. CD8+ responses (and no CD4+ responses) were detected in 3/26 subjects using chromium release assay and in 2/42 subjects using IFN-γ ELISPOT assay.
• This epitope was included in the vaccine.

References

Gorse2008a Geoffrey J. Gorse, Lindsey R. Baden, Margaret Wecker, Mark J. Newman, Guido Ferrari, Kent J. Weinhold, Brian D. Livingston, Tonya L. Villafana, Hongli Li, Elizabeth Noonan, Nina D. Russell, and HIV Vaccine Trials Network. Safety and Immunogenicity of Cytotoxic T-Lymphocyte Poly-Epitope, DNA Plasmid (EP HIV-1090) Vaccine in Healthy, Human Immunodeficiency Virus Type 1 (HIV-1)-Uninfected Adults. Vaccine, 26(2):215-223, 10 Jan 2008. PubMed ID: 18055072. Show all entries for this paper.

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Displaying record number 1835

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords	dendritic cells

Notes

• The role of CD4+ T-cell help in expansion of virus-specific memory CTL was studied through co-culture ex vivo
• Optimal expansion of HIV-1-specific memory CTL depended on CD4+ T cell help in 9 of 10 patients -- CD40 ligand trimer (CD40LT) could enhance CTL in the absence of CD4+ T cell help to a variable degree in most of patients.
• Those CTL that didn't respond to CD40LT could expand with IL2 present, and IL15 produced by dendritic cells also contributes.
• The T-helper epitope used for CD4+ T cell stimulation was the universal tetanus helper epitope TET830-843 (QYIKANSKFIGITE)

References

Ostrowski2000 M. A. Ostrowski, S. J. Justement, L. Ehler, S. B. Mizell, S. Lui, J. Mican, B. D. Walker, E. K. Thomas, R. Seder, and A. S. Fauci. The role of CD4+ T cell help and CD40 ligand in the in vitro expansion of HIV-1-specific memory cytotoxic CD8+ T cell responses. J. Immunol., 165(11):6133-41, 1 Dec 2000. URL: http://www.jimmunol.org/cgi/content/full/165/11/6133. PubMed ID: 11086046. Show all entries for this paper.

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Displaying record number 57345

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Subtype	B
Species (MHC/HLA)	human(A*02:01)
Immunogen	peptide-HLA interaction
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Other
Keywords	dendritic cells

Notes

• Challenge peptides loaded onto mature dendritic cells (DC) elicited HIV-1 specific T-cell functions (including IFN-gamma production, CD8+ and CD4+ T-cell proliferation as well as polyfunctional T-cell response) that were greater than responses to peptides alone or peptides loaded onto immature DC.
• IV9 along with 2 other HIV-1 epitopes was mixed in with an EBV challenge epitope to study whether it competes or interferes with T-cell reactivity - it did not.

References

Huang2009 Xiao-Li Huang, Zheng Fan, LuAnn Borowski, and Charles R. Rinaldo. Multiple T-Cell Responses to Human Immunodeficiency Virus Type 1 Are Enhanced by Dendritic Cells. Clin. Vaccine Immunol., 16(10):1504-1516, Oct 2009. PubMed ID: 19692626. Show all entries for this paper.

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Displaying record number 57515

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Species (MHC/HLA)	human(A*02:01)
Immunogen	in vitro stimulation or selection
Experimental methods	Tetramer binding
Keywords

Notes

• The study investigated the effect of blocking interleukin-10 (IL-10) on HIV-specific CTL responses. PBMCs from viremic and aviremic patients were stimulated with optimal HIV epitopes in the presence of IL-10 receptor antibody. Blocking the receptor increased the number of HIV-specific CTLs, and the effect was higher in viremic than in aviremic patients.
• This epitope was one of 12 known optimal epitopes used to stimulate PBMC from viremic and aviremic patients in order to test the effect of blocking IL-10.

References

Brockman2009 Mark A. Brockman, Douglas S. Kwon, Daniel P. Tighe, David F. Pavlik, Pamela C. Rosato, Jennifer Sela, Filippos Porichis, Sylvie Le Gall, Michael T. Waring, Kristin Moss, Heiko Jessen, Florencia Pereyra, Daniel G. Kavanagh, Bruce D. Walker, and Daniel E. Kaufmann. IL-10 Is Up-Regulated in Multiple Cell Types During Viremic HIV Infection and Reversibly Inhibits Virus-Specific T Cells. Blood, 114(2):346-356, 9 Jul 2009. PubMed ID: 19365081. Show all entries for this paper.

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Displaying record number 52172

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(309-317)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	RT2
Species (MHC/HLA)	human, transgenic mouse(A*02:01)
Immunogen	vaccine
Experimental methods
Keywords

Vaccine Details

Vaccine type	HIV-1 peptide in filamentous bacteriophage major coat protein
Vaccine component	RT

Notes

• HLA-A2 transgenic mice were injected with bacteriophage antigens expressing a Th epitope and the HIV CTL epitope ILKEPVHGV, and epitope-specific cytotoxic activity was induced.

References

Guardiola2001 J. Guardiola, P. De Berardinis, R. Sartorius, C. Fanutti, R. N. Perham, and G. Del Pozzo. Phage Display of Epitopes from HIV-1 Elicits Strong Cytolytic Responses In Vitro and In Vivo. Adv. Exp. Med. Biol., 495:291-298, 2001. PubMed ID: 11774581. Show all entries for this paper.

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Displaying record number 507

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords	TCR usage

Notes

• HIV+ individuals were followed longitudinally using MHC tetramers in combination with 14 anti-BV chain MAbs, and clonal expansion of HIV-specific T cells was followed in vivo.
• Seven HIV+ people were studied, and all showed expansions of particular TCR BV clones, often several, relative to uninfected controls.
• Three patients were followed in detail, TCR VB expansions persisted for 2 to 3 years, with occasional transient increases.

References

Wilson1998 J. D. Wilson, G. S. Ogg, R. L. Allen, P. J. Goulder, A. Kelleher, A. K. Sewell, C. A. O'Callaghan, S. L. Rowland-Jones, M. F. Callan, and A. J. McMichael. Oligoclonal Expansions of CD8+ T Cells in Chronic HIV Infection Are Antigen Specific. J. Exp. Med., 188(4):785-790, 1998. PubMed ID: 9705961. Show all entries for this paper.

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Displaying record number 58002

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location
Epitope	ILKEPVHGV	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Country	South Africa, United Kingdom
Experimental methods	CD8 T-cell Elispot - IFNγ, Tetramer binding
Keywords	computational epitope prediction, optimal epitope

Notes

• A prediction tool, HLArestrictor, was developed to predict minimal epitopes from longer peptides. Minimal epitopes were predicted and validated for 18 EliSpot-positive 18mers.
• ILKEPVHGV was predicted from EliSpot-positive 18mer ELAENREILKEPVHGVYY. The epitope was validated in two A*0201-positive HIV-positive individuals by tetramer staining.

References

ErupLarsen2011 Malene Erup Larsen, Henrik Kloverpris, Anette Stryhn, Catherine K. Koofhethile, Stuart Sims, Thumbi Ndung'u, Philip Goulder, Søren Buus, and Morten Nielsen. HLArestrictor---A Tool for Patient-Specific Predictions of HLA Restriction Elements and Optimal Epitopes within Peptides. Immunogenetics, 63(1):43-55, Jan 2011. PubMed ID: 21079948. Show all entries for this paper.

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Displaying record number 58640

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(464-472)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	Pol464-472
Subtype	B
Species (MHC/HLA)	human(A*02:01)
Immunogen	peptide-HLA interaction
Country	United States
Experimental methods	Chromium-release assay
Keywords	enhancing activity

Notes

• Since HIV-1 infected peripheral dendritic cells (DCs) are functionally impaired in their role as antigen presenting cells (APCs), novel CTL responses in an asymptomatic HIV-patient were primed by using blood-derived DCs from healthy donors as APCs instead. Both epitope peptides and endogenously processed epitope antigen were now recognizable.
• CTL from an HLA-A*0201 positive subject reacted to previously characterized peptide ILKEPVHGV.

References

Dupuis1997 M. Dupuis, M. V. Peshwa, C. Benike, S.K> Kundu, E. G. Engleman, W. C. Van Schooten, and T. C. Merigan. Allogeneic Dendritic Cell Induction of HIV-Specific Cytotoxic T Lymphocyte Responses from T Cells of HIV Type 1-Infected and Uninfected Individuals. AIDS Res. Hum. Retroviruses, 13:33-39, 1997. The potential benefit of T cell-based vaccination for HIV-1 infection remains to be determined. Cytotoxic T lymphocytes (CTLs) appear to clear substantial populations of HIV-1 virus in vivo, although CTL activity may contribute to the decline in CD4+ T cell count observed in the course of the disease. To investigate further the role of specific CTL responses in the control of HIV-1 replication, we raised primary CTL lines against a panel of conserved HIV-1 epitopes using blood-derived dendritic cells as antigen-presenting cells (APCs). Specific primary human CTL responses were induced against HLA-A*0201-restricted peptides with dendritic cells from HIV-1-seronegative donors. This method of immunization elicited cytotoxic activities capable of recognizing endogenously processed antigen. The CTL induction protocol was extended in order to explore the capacity of HLA-matched allogeneic dendritic cells to evoke novel CTL responses in T cells from an HIV-seropositive asymptomatic individual. Allogeneic peptide-pulsed dendritic cells from a healthy sibling were capable of eliciting a CTL response directed against an HIV epitope (env814: SLLNATDIAV) that was initially not detected in the CTL effector population of the HIV-1- infected patient. The possibility of manipulating CTL specificity directed against multiple conserved HIV-1 epitopes represents a significant step in the evaluation of T cell-based vaccination for treatment of disease. PubMed ID: 8989425. Show all entries for this paper.

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Displaying record number 502

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

• High levels of CD8+ HIV-1 specific and cytomegalovirus specific CTL were detected by HLA-A*0201-peptide tetramers in 3 infected subjects with very low CD4 counts, but CD8 T cell mediated effector activity was not seen.
• Thus HIV-1 specific CD8+ cells may be present but may lack direct effector activity in late disease, suggesting that overcoming antigen unresponsiveness may be a useful therapeutic strategy.

References

Spiegel2000 H. M. Spiegel, G. S. Ogg, E. DeFalcon, M. E. Sheehy, S. Monard, P. A. Haslett, G. Gillespie, S. M. Donahoe, H. Pollack, W. Borkowsky, A. J. McMichael, and D. F. Nixon. Human Immunodeficiency Virus Type 1- and Cytomegalovirus-Specific Cytotoxic T Lymphocytes Can Persist at High Frequency for Prolonged Periods in the Absence of Circulating Peripheral CD4+ T Cells. J. Virol., 74:1018-1022, 2000. PubMed ID: 10623767. Show all entries for this paper.

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Displaying record number 52779

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Experimental methods	Tetramer binding
Keywords	genital and mucosal immunity

Notes

• Lymphocytes from rectal biopsies were used to characterize the CD8+ T cell response to HIV in GALT, Gut-associated lymphoid tissues. Patients were selected on the basis of being HLA-A2+ and having detectable SLYNTVATL and ILKEPVHGV tetramer responses in PBMC. SLYNTVATL frequency was increased in GALT relative to PBMC in 6/7 patients studied, while a control response to a CMV-peptide was diminished in GALT. Only two patients had ILKEPVHGV CD8+ T cell responses, and both had slightly higher frequencies in GALT than PBMC.
• HIV may perturb lymphocyte retention in GALT, suggested by an overall reduction of GALT CD8+ cells expressing alphaEbeta7. GALT HIV-specific CD8+ T cells expressed alphaEbeta7, suggesting mucosal priming.

References

Shacklett2003 Barbara L. Shacklett, Catherine A. Cox, Johan K. Sandberg, Neil H. Stollman, Mark A. Jacobson, and Douglas F. Nixon. Trafficking of Human Immunodeficiency Virus Type 1-Specific CD8+ T Cells to Gut-Associated Lymphoid Tissue During Chronic Infection. J. Virol., 77(10):5621-5631, May 2003. PubMed ID: 12719554. Show all entries for this paper.

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Displaying record number 503

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords	epitope processing, immunodominance

Notes

• Proteasome regulation influences epitope processing and could influence immunodominance.
• The proteasome is inhibited by lactacystin treatment, and gamma IFN induces expression of proteasome subunits, LMP2 and LMP7, which combine with the proteasome to create an immunoproteasome.
• IFN-gamma induction of the immunoproteasome and lactacystin inhibition increases the presentation of the A*0201 VIYQYMDDL epitope, but decreases the presentation of the A*0201 ILKEPVHGV epitope, which is immunodominant within pol proteins, showing the two epitopes are processed by different pathways.
• ILKEPVHGV seems to be processed by the classical proteasome pathway, while VIYQYMDDL appears to be destroyed by this pathway.
• This epitope contains the catalytic site (YMDD) of RT, a conserved sequence in HIV-1 which restricts escape mutants.

References

Sewell1999 A. K. Sewell, D. A. Price, H. Teisserenc, B. L. Booth, U. Gileadi, F. M. Flavin, J. Trowsdale, R. E. Phillips, and V. Cerundolo. IFN-gamma Exposes a Cryptic Cytotoxic T Lymphocyte Epitope in HIV-1 Reverse Transcriptase. J. Immunol., 162:7075-7079, 1999. PubMed ID: 10358150. Show all entries for this paper.

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Displaying record number 504

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords	epitope processing

Notes

• The ILKEPVHGV was modified by the addition of an N-palmitoyl-lysine residue at the P0, P1 or P10 positions of the parent peptide to create a lipopeptide for direct antigen delivery to the cytoplasm for processing.
• The N-terminal modification increased the life span for functional CTL recognition up to 48 hours in comparison to the parent peptide.

References

Loing2000 E. Loing, M. Andrieu, K. Thiam, D. Schorner, K. H. Wiesmuller, A. Hosmalin, G. Jung, and H. Gras-Masse. Extension of HLA-A*0201-Restricted Minimal Epitope by N epsilon-Palmitoyl-Lysine Increases the Life Span of Functional Presentation to Cytotoxic T Cells. J. Immunol., 164:900-907, 2000. PubMed ID: 10623838. Show all entries for this paper.

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Displaying record number 53006

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(309-317 MN)
Epitope	ILKEPVHGV	Epitope Alignment
Subtype	B
Species (MHC/HLA)	humanized mouse(A*02:01)
Immunogen	vaccine
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	epitope processing, vaccine-induced immune responses, immunodominance, immunotherapy

Vaccine Details

Vaccine type	DNA, polyepitope
Vaccine strain	B clade MN
Vaccine component	gp120, Protease, RT
Adjuvant	Incomplete Freund's Adjuvant (IFA)

Notes

• Immunization of HLA-A*0201-transgenic mice with synthetic genes encoding clusters of human A*0201 CTL epitopes located at the sites of drug resistance mutations, induced RT-specific cellular responses indicating the immunogenicity of these constructs. This vaccine strategy may be a first step towards a therapeutic vaccine against drug-resistant strains.
• This was one of five HLA-A*0201 epitopes from the RT or protease proteins that was included in the polyepitope vaccine. When the transgenic HLA A*0202 mice were vaccinated with the polyepitope construct or with a mixture of RT peptides, a sustained low level CD8+ T-cell gamma IFN response was observed, in contrast to when an intact RT gene was used for vaccination.

References

Isaguliants2004 Maria G. Isaguliants, Bartek Zuber, Andreas Boberg, Dan Sjöstrand, Sergey V. Belikov, Erik Rollman, Anne Kjerrström Zuber, Vladimir O. Rechinsky, Ann-Sofie Rytting, Clas F. R. Källander, Jorma Hinkula, Sergey N. Kochetkov, Margaret Liu, and Britta Wahren. Reverse Transcriptase-Based DNA Vaccines against Drug-Resistant HIV-1 Tested in a Mouse Model. Vaccine, 22(13-14):1810-1819, 16 Apr 2004. PubMed ID: 15068865. Show all entries for this paper.

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Displaying record number 53009

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location
Epitope	ILKEPVHGV	Epitope Alignment
		Show epitope variants
Epitope Name	IV9
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay, T-cell Elispot
Keywords	epitope processing, escape, kinetics, variant cross-reactivity

Notes

• Epitope escape mutations in chronically infected individuals developed over several years indicating slight selective advantage of escape mutants. The maturation state of CTLs appear to affect the rate of epitope mutation and CTL decay.
• In two patients, IV9 mutations preceded the loss of IV9-specific CD8+ T-cells. In a third patient, escape mutations were coincident with IV9-specific CD8+ T-cell loss. One patient was infected with a ilepvhgA variant, and transiently reverted to the consensus form at year 3. One patient never made a response to IV9 despite being infected with the consensus form of the epitope.

References

Jamieson2003 Beth D. Jamieson, Otto O. Yang, Lance Hultin, Mary Ann Hausner, Patricia Hultin, Jose Matud, Kevin Kunstman, Scott Killian, John Altman, Kristina Kommander, Bette Korber, Janis Giorgi, and Steven Wolinsky. Epitope Escape Mutation and Decay of Human Immunodeficiency Virus Type 1-Specific CTL Responses. J. Immunol., 171(10):5372-5379, 15 Nov 2003. PubMed ID: 14607940. Show all entries for this paper.

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Displaying record number 53011

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Gag
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Subtype	B
Species (MHC/HLA)	human(A*02:01)
Immunogen	in vitro stimulation or selection
Experimental methods	Chromium-release assay, Flow cytometric T-cell cytokine assay, Tetramer binding
Keywords	epitope processing, rate of progression, immunodominance, acute/early infection, dendritic cells, TCR usage, memory cells

Notes

• In contrast to IV9-CTLs, SL9-CTLs were shown to be primed by immature DCs and to be independent of help from CD4+ or exogenous IL2 and sensitive to paracrine IL-2-induced apoptosis.

References

Kan-Mitchell2004 June Kan-Mitchell, Brygida Bisikirska, Flossie Wong-Staal, Keri L. Schaubert, Melissa Bajcz, and Michal Bereta. The HIV-1 HLA-A2-SLYNTVATL Is a Help-Independent CTL Epitope. J. Immunol., 172(9):5249-5261, 1 May 2004. PubMed ID: 15100263. Show all entries for this paper.

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Displaying record number 536

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	transgenic mouse(A*02:01)
Immunogen	vaccine
Experimental methods
Keywords

Vaccine Details

Vaccine type	DNA

Notes

• A minigene vaccine construct encoding 6 HLA 2.1 and 3 HLA A11 restricted CTL epitopes, the universal Th cell epitope PADRE (pan-DR epitope) and an ER translocating signal sequence was constructed.
• The epitopes were chosen for dominant recognition by CTLs during HBV and HIV infections in humans.
• HLA transgenic mice were used for quantitating in vivo immunogenicity of DNA vaccines encoding HLA-restricted CTL epitopes -- strong responses were observed to all nine epitopes, and CTL memory persisted up to four months after a single injection.

References

Ishioka1999 G. Y. Ishioka, J. Fikes, G. Hermanson, B. Livingston, C. Crimi, M. Qin, M. F. del Guercio, C. Oseroff, C. Dahlberg, J. Alexander, R. W. Chesnut, and A. Sette. Utilization of MHC Class I Transgenic Mice for Development of Minigene. J. Immunol., 162:3915-3925, 1999. PubMed ID: 10201910. Show all entries for this paper.

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Displaying record number 516

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	in vitro stimulation or selection
Experimental methods
Keywords	binding affinity

Notes

• This epitope was included as a positive control.
• Binding affinity to A*0201 was measured, C_{1/2 max} µM =12.

References

Konya1997 J. Konya, G. Stuber, A. Bjorndal, E. M. Fenyo, and J. Dillner. Primary induction of human cytotoxic lymphocytes against a synthetic peptide of the human immunodeficiency virus type 1 protease. J. Gen. Virol., 78:2217-2224, 1997. PubMed ID: 9292009. Show all entries for this paper.

Menendez-Arias1998 L. Menendez-Arias, A. Mas, and E. Domingo. Cytotoxic T-Lymphocyte Responses to HIV-1 Reverse Transcriptase. Viral Immunol., 11:167-181, 1998. PubMed ID: 10189185. Show all entries for this paper.

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Displaying record number 538

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

• Of 17 infected HLA A*0201 subjects, 13 had CTL responses against the p17 SLYNTVATL epitope, six recognized ILKEPVHGV and five recognized VIYQYMDDL, and there was no correlation between viral load and recognition of a specific epitope or evidence of immune escape.
• Only one subject had CTL against all three epitopes.
• Subjects were part of the San Francisco City Clinic Cohort, the ARIEL project and from the Boston area.
• C. Brander notes this is an A*0201 epitope.

References

Brander1998 Christian Brander, Kelly E. Hartman, Alicja K. Trocha, Norman G. Jones, R. Paul Johnson, Bette Korber, Peggy Wentworth, Susan P. Buchbinder, Steve Wolinsky, Bruce D. Walker, and Spyros A. Kalams. Lack of Strong Immune Selection Pressure by the Immunodominant, HLA-A*0201-Restricted Cytotoxic T Lymphocyte Response in Chronic Human Immunodeficiency Virus-1 Infection. J. Clin. Invest., 101(11):2559-2566, 1 Jun 1998. PubMed ID: 9616227. Show all entries for this paper.

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Displaying record number 539

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART

Notes

• CTL effector levels were measured after potent ARV therapy using HLA-tetramer complexes for the A*0201 epitopes SYLVTVATL and ILKEPVHGV in seven patients, and the B*3501 epitope DPNPQEVVL in one additional patient.
• Levels of CTL effectors typically decline for 5-7 days and then rebound, fluctuating during the first two weeks of therapy.
• After the early fluctuation, there was a steady exponential decay with a median half-life of 45 days.

References

Ogg1999 G. S. Ogg, X. Jin, S. Bonhoeffer, P. Moss, M. A. Nowak, S. Monard, J. P. Segal, Y. Cao, S. L. Rowland-Jones, A. Hurley, M. Markowitz, D. D. Ho, A. J. McMichael, and D. F. Nixon. Decay Kinetics of Human Immunodeficiency Virus-Specific Effector Cytotoxic T Lymphocytes after Combination Antiretroviral Therapy. J. Virol., 73:797-800, 1999. PubMed ID: 9847391. Show all entries for this paper.

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Displaying record number 1228

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484 LAI)
Epitope	ILKEPVHGV	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords	optimal epitope, A-list

Notes

• C. Brander notes this is a A*0201 epitope.

References

Llano2019 Anuska Llano, Samandhy Cedeño, Sandra Silva Arrieta, and Christian Brander. The 2019 Optimal HIV CTL Epitopes Update: Growing Diversity in Epitope Length and HLA restriction. 2019. Show all entries for this paper.

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Displaying record number 53443

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(468-476 IIIB)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	pol468-476
Subtype	B
Species (MHC/HLA)	humanized mouse(A*02:01)
Immunogen	vaccine
Experimental methods	Intracellular cytokine staining
Keywords	epitope processing, vaccine-induced immune responses, variant cross-reactivity, vaccine antigen design

Vaccine Details

Vaccine type	DNA
Vaccine strain	B clade IIIB
Vaccine component	Gag-Pol

Notes

• When A*0201-C3H/J transgenic mice were immunized with plasmids encoding wild-type gag-pol, codon-optimized (CO) gag-pol, and an expression library vaccine expressing 16 fragments of gag-pol fused with ubiquitin for proteosome targeting (ELI), the ELI vaccine produced up to 10-fold higher CD8 T-cell responses than the other two vaccines. In contrast to the wt and CO vaccines, which tended to augment only immunodominant responses, boosting with the ELI vaccine resulted in many CD8 responses against variant epitopes from different HIV-1 clades, and against drug-resistant variants.
• This epitope was recognized in transgenic mice vaccinated with all three vaccine constructs, but the most intense responses were to the ELI vaccine.

References

Singh2004 Rana A K Singh and Michael A Barry. Repertoire and Immunofocusing of CD8 T Cell Responses Generated by HIV-1 gag-pol and Expression Library Immunization Vaccines. J. Immunol., 173(7):4387-4393, 1 Oct 2004. PubMed ID: 15383568. Show all entries for this paper.

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Displaying record number 505

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(510-518)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	vaccine
Experimental methods
Keywords

Vaccine Details

Vaccine type	canarypox, vaccinia
Vaccine component	Env, Gag, Nef, Pol

Notes

• ELISPOT was used to assay the CD8 T cell response to the HIV-1 proteins Gag, Pol, Nef or Env expressed in vaccinia or canarypox vectors in 19 HIV+ people.
• The highest CTL frequency was directed at epitopes in Pol.
• In A*0201 individuals, higher numbers of spot-forming T cells were directed against HIV-1 proteins expressed in vaccinia than to peptides SLYNTVATL and ILKEPVHGV presented by A2.

References

Larsson1999 M. Larsson, X. Jin, B. Ramratnam, G. S. Ogg, J. Engelmayer, M. A. Demoitie, A. J. McMichael, W. I. Cox, R. M. Steinman, D. Nixon, and N. Bhardwaj. A Recombinant Vaccinia Virus Based ELISPOT Assay Detects High Frequencies of Pol-Specific CD8 T Cells in HIV-1-Positive Individuals. AIDS, 13:767-777, 1999. PubMed ID: 10357375. Show all entries for this paper.

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Displaying record number 1354

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Species (MHC/HLA)	human(A*02:01)
Immunogen	in vitro stimulation or selection, HIV-1 infection
Experimental methods
Keywords

Notes

• Integration of HIV RT CTL epitopes into the N-terminus of the HLA-A2 heavy chain, or tethering the epitopes to the target chain, resulted in epitope-specific lysis by CD8+ CTL.
• These antigens could also be used to stimulate primary responses in vitro.

References

DelaCruz2000 C. S. Dela Cruz, R. Tan, S. L. Rowland-Jones, and B. H. Barber. Creating HIV-1 reverse transcriptase cytotoxic T lymphocyte target structures by HLA-A2 heavy chain modifications. Int. Immunol., 12(9):1293-302, Sep 2000. URL: http://intimm.oupjournals.org/cgi/content/full/12/9/1293. PubMed ID: 10967024. Show all entries for this paper.

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Displaying record number 53608

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(464-472)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Subtype	B
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	8183A: A*02:01, A*03:01, B*35:01, B*51, C*04, C*06
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, Intracellular cytokine staining
Keywords	dynamics, acute/early infection

Notes

• Patients with acute or early infection were shown to preferentially target variable peptides with higher entropy while those with chronic infection showed responses towards more conserved peptides with lower entropy. In longitudinally followed subjects, responses to variable proteins declined over time while responses to conserved proteins increased. The decline is suggested to be due to CTL escape.
• The response to this epitope was not detected until month 25 and increased over time.

References

Bansal2005a Anju Bansal, Ethan Gough, Steffanie Sabbaj, Doug Ritter, Karina Yusim, Greg Sfakianos, Grace Aldrovandi, Richard A. Kaslow, Craig M. Wilson, Mark J. Mulligan, J. Michael Kilby, and Paul A. Goepfert. CD8 T-Cell Responses in Early HIV-1 Infection Are Skewed Towards High Entropy Peptides. AIDS, 19(3):241-250, 18 Feb 2005. PubMed ID: 15718834. Show all entries for this paper.

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Displaying record number 519

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(468-476)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	in vitro stimulation or selection
Experimental methods
Keywords

Notes

• Immunogenic in humans, slow dissociation rate, and associated with immunogenicity in transgenic HLA-A*0201/K^b mice.
• CTL generated by in vitro stimulation of PBMC derived from uninfected individual.

References

vanderBurg1996 S. H. van der Burg, M. J. W. Visseren, R. M. P. Brandt, W. M. Kast, and C. J. M. Melief. Immunogenicity of Peptides Bound to MHC Class I Molecules Depends on the MHC-Peptide Complex Stability. J. Immunol., 156:3308-3314, 1996. Peptide-MHC dissociation rate is highly correlated with immunogenicity. In this study, HLA-A*0201 restricted epitopes from HPV, HBV and HIV were studied, some in the context of immunogenicity in peptide immunized HLA-A*0201/K$^b$ transgenic mice. PubMed ID: 8617954. Show all entries for this paper.

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Displaying record number 53796

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	I9V
Species (MHC/HLA)	transgenic mouse(A*02:01)
Immunogen	vaccine
Experimental methods	Chromium-release assay, Flow cytometric T-cell cytokine assay
Keywords	memory cells, vaccine antigen design, characterizing CD8+ T cells

Vaccine Details

Vaccine type	measles virus (MV)
Vaccine strain	multiple epitope immunogen
Vaccine component	gp140, gp140ΔV3

Notes

• A recombinant measles MVSchw virus expressing an HIV-1-derived polyepitope effectively primed HLA-A*0201-restricted CTL responses against multiple conserved HIV-1 epitopes in HLA-A*0201 transgenic mice. Also, a recombinant MVSchw virus expressing gp140 with deleted V1, V2, and V3 loops successfully induces neutralizing antibodies against HIV-1. A live attenuated measles vaccine could provide a safe and efficient pediatric vaccination vector for simultaneous vaccination against HIV and measles.

References

Lorin2005a Clarisse Lorin, Frédéric Delebecque, Valérie Labrousse, Lucie Da Silva, François Lemonnier, Michel Brahic, and Frédéric Tangy. A Recombinant Live Attenuated Measles Vaccine Vector Primes Effective HLA-A0201-Restricted Cytotoxic T Lymphocytes and Broadly Neutralizing Antibodies against HIV-1 Conserved Epitopes. Vaccine, 23(36):4463-4472, 22 Aug 2005. PubMed ID: 15993518. Show all entries for this paper.

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Displaying record number 520

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(468-476)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	in vitro stimulation or selection
Experimental methods
Keywords

Notes

• Binds HLA-A*0201 -- CTL generated by in vitro stimulation of PBMC from an HIV negative donor.

References

vanderBurg1995 S. H. van der Burg, M. R. Klein, C. J. Van de Velde, W. M. Kast, F. Miedema, and C. J. Melief. Induction of a Primary Human Cytotoxic T Lymphocyte Response against a Novel Conserved Epitope in a Functional Sequence of HIV-1 Reverse Transcriptase. AIDS, 9:121-127, 1995. PubMed ID: 7536421. Show all entries for this paper.

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Displaying record number 1474

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(309-317)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	P1
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART, escape

Notes

• The epitope was recognized by patient 250#0 but not in another A*0201+ patient, 201#5, in a study of the effects of therapy escape mutations on CTL recognition.

References

Samri2000 A. Samri, G. Haas, J. Duntze, J. M. Bouley, V. Calvez, C. Katlama, and B. Autran. Immunogenicity of mutations induced by nucleoside reverse transcriptase inhibitors for human immunodeficiency virus type 1-specific cytotoxic T cells. J. Virol., 74(19):9306-12, Oct 2000. URL: http://jvi.asm.org/cgi/content/full/74/19/9306. PubMed ID: 10982378. Show all entries for this paper.

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Displaying record number 54299

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Subtype	B
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Country	China
Experimental methods	CD8 T-cell Elispot - IFNγ, Tetramer binding
Keywords	HAART, ART, responses in children, dendritic cells

Notes

• Immune responses in HIV-1 infected children either undregoing HAART or not were analysed. HIV-specific CTLs were lower in children responding to HAART than in non-responders and HAART-naive children. CTL frequency was correlated with myeloid DC frequency in treatment-naive patients, and inversely correlated with duration of virus supression following treatment.
• 11 of the 22 children had significant responses to SL9.

References

Zhang2006 Zheng Zhang, Qing-xia Zhao, Jun-liang Fu, Jin-xia Yao, Yun He, Lei Jin, and Fu-sheng Wang. Characteristics of HIV-1-Specific CD8 T-Cell Responses and Their Role in Loss of Viremia in Children Chronically Infected with HIV-1 Undergoing Highly Active Antiretroviral Therapy. Chin. Med. J., 119(23):1949-1957, 5 Dec 2006. PubMed ID: 17199938. Show all entries for this paper.

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Displaying record number 521

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

• Mutational study: position 1 I to Y increases complex stability with HLA-A*0201.

References

Menendez-Arias1998 L. Menendez-Arias, A. Mas, and E. Domingo. Cytotoxic T-Lymphocyte Responses to HIV-1 Reverse Transcriptase. Viral Immunol., 11:167-181, 1998. PubMed ID: 10189185. Show all entries for this paper.

Pogue1995 R. R. Pogue, J. Eron, J. A. Frelinger, and M. Matsui. Amino-Terminal Alteration of the HLA-A*0201-Restricted Human Immunodeficiency Virus Pol Peptide Increases Complex Stability and In Vitro Immunogenicity. Proc. Natl. Acad. Sci. U.S.A., 92:8166-8170, 1995. In this mutational study a substitution of 476 I to Y did not increase affinity but did increase complex stability with HLA-A*0201. The altered peptide (Y) provided a greater stimulation of wildtype pol-specific CTL response relative to the wildtype peptide (I), in three different seropositive individuals. PubMed ID: 7545295. Show all entries for this paper.

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Displaying record number 52702

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Subtype	B
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Experimental methods	Chromium-release assay, Cytokine production, Intracellular cytokine staining, Proliferation, Tetramer binding
Keywords

Notes

• Telomer length is short in the CD8+ T-cell compartment of HIV-1 infected people, indicating excessive CTL activation and premature senescense. Here human telomerase RT (hTERT) transduction of HIV-1-specific CTL was used to study the functional impact of telomerase. Telomerase expression enhanced proliferative capacity, as well as cytolytic and antiviral capabilities; cytokine production was unchanged. hTERT transduced CTLs were 10-fold more efficient in controlling HIV-1 replication in culture. Thus telomerase transduction can restore CTL mediated cytolysis, and may have therapeutic potential.
• Three polyclonal CD8+ T-cell lines derived from an HIV-1, HLA A*0201 positive patient were used in this study, including one specific for this epitope. An IV9-specific monoclonal cell line, 68A62 was also generated.

References

Dagarag2003 Mirabelle Dagarag, Hwee Ng, Rachel Lubong, Rita B. Effros, and Otto O. Yang. Differential Impairment of Lytic and Cytokine Functions in Senescent Human Immunodeficiency Virus Type 1-Specific Cytotoxic T Lymphocytes. J. Virol., 77(5):3077-3083, Mar 2003. PubMed ID: 12584333. Show all entries for this paper.

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Displaying record number 52704

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(464-472)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	I9V
Subtype	B
Species (MHC/HLA)	transgenic mouse(A*02:01)
Immunogen	vaccine
Experimental methods	Chromium-release assay, Cytokine production, Intracellular cytokine staining, Tetramer binding
Keywords

Vaccine Details

Vaccine type	peptide
Vaccine component	RT
Adjuvant	CpG immunostimulatory sequence (ISS)

Notes

• HLA-A*0201 transgenic mice were immunized with a Th-CTL-fusion peptide composed of the I9V CTL epitope linked to the promiscuous PADRE Th epitope. The peptide only when given in combination with CpG elicited strong I9V-CTL responses.
• The peptide-CpG vaccinated mice, when challenged with pol embedded in vaccinia (pol-vv), could clear the virus from the ovaries. Additionally, intranasal immunized mice given an intranasal pol-vv challenge reduced virus in the lungs.

References

Daftarian2003 Pirouz Daftarian, Saima Ali, Rahul Sharan, Simon F. Lacey, Corinna La Rosa, Jeff Longmate, Christopher Buck, Robert F. Siliciano, and Don J. Diamond. Immunization with Th-CTL Fusion Peptide and Cytosine-Phosphate-Guanine DNA in Transgenic HLA-A2 Mice Induces Recognition of HIV-Infected T Cells and Clears Vaccinia Virus Challenge. J. Immunol., 171(8):4028-4039, Oct 2003. PubMed ID: 14530323. Show all entries for this paper.

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Displaying record number 532

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(464-472)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART

Notes

• Peptide-tetramer complexes of A*0201 and SLYNTVATL or ILKEPVHGV were used to study individuals receiving HAART to determine the frequency of Class I HLA-restricted anti-HIV CD8+ T cells.
• 17/18 asymptomatic patients had a CTL response to one or both epitopes -- 72% had a CTL response to SLYNTVATL.
• After HAART, the majority of the epitope-specific CTL were apparently memory cells.

References

Gray1999 C. M. Gray, J. Lawrence, J. M. Schapiro, J. D. Altman, M. A. Winters, M. Crompton, M. Loi, S. K. Kundu, M. M. Davis, and T. C. Merigan. Frequency of Class I HLA-Restricted Anti-HIV CD8+ T Cells in Individuals Receiving Highly Active Antiretroviral Therapy (HAART). J. Immunol., 162:1780-1788, 1999. PubMed ID: 9973442. Show all entries for this paper.

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Displaying record number 59172

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	pol 476-484
Subtype	B
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Country	France
Experimental methods	CD8 T-cell Elispot - IFNγ, CTL suppression of replication, HLA binding, Intracellular cytokine staining, Other
Keywords	binding affinity, elite controllers

Notes

• 49 HLA-B*57⁺ and 52 HLA-B*57^- ART-naive HIV controllers (HIC) from the French ANRS CODEX cohort were compared to determine various impacts of B*57 and non-B*57 alleles on HIV-specific CTL responses (e.g. activation and differentiation markers, proliferation potential, cytokine production and HIV-suppression). HLA-B*57⁺ chronic progressors were the control group.
• CTL response was higher in HLA-B*57⁺ than -B*57^- subjects, most of them Gag-specific. 80% of all such responses were restricted by -B*57^- Gag or Nef epitopes.
• Greater frequency of as well as stronger CTL responses correlated with higher functional avidity of TCR-peptide interaction. B*57-restricted responses were 1 log more sensitive than non-B*57-restricted responses regardless of whether subjects were HLA-B*57⁺ or -B*57^-, and led to higher proliferation of CTL, higher IL-2 production, higher frequency of IFN-γ-producing cells, higher degree of differentiation with more CD127 (and as seen by higher markers for central memory cells, CCR7⁺CD45RO⁺ / effector memory cells, CCR7⁺CD27⁺CD45RO⁺ / senescent cells, CD57⁺). Activation markers CD38 and HLA-DR however, remained the same between CTL restricted by HLAs -B*57 or not.
• Higher TCR-peptide avidity was correlated also to HICs as compared to progressors - with proliferation, IL-2 production and CD127 levels being affected in HLA-B*57-restricted responding CTL.
• Viral replication suppression was seen in all HIC whether HLA-B*57⁺ or -B*57^-. Strong viral suppression (SVS) correlates with lower plasma viral load.
• HLA-A*0201-restricted peptide pol 476-484, ILKEPVHGV, was recognized by 4/21 B*57⁺ subjects with a mean intensity ˜500 Sfc/10⁶ PBMCs and <500 Sfc/10⁶ ml for 4/22 B*57^- subjects.

References

Lecuroux2014 Camille Lécuroux, Asier Sáez-Cirión, Isabelle Girault, Pierre Versmisse, Faroudy Boufassa, Véronique Avettand-Fenoël, Christine Rouzioux, Laurence Meyer, Gianfranco Pancino, Olivier Lambotte, Martine Sinet, and Alain Venet. Both HLA-B*57 and Plasma HIV RNA Levels Contribute to the HIV-Specific CD8+ T Cell Response in HIV Controllers. J. Virol., 88(1):176-187, Jan 2014. PubMed ID: 24131719. Show all entries for this paper.

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Displaying record number 508

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords	immunodominance

Notes

• Only 4/11 HLA-A2+ HIV+ individuals had CTL that reacted to SLYNTVATL, calling into question whether it is immunodominant.
• 95 optimally-defined peptides from this database were used to screen for INFγ responses to other epitopes.
• 2/11 of the A2+ individuals responded to ILKEPVHGV, and neither of these two responded to SLYNTVATL.

References

Betts2000 M. R. Betts, J. P. Casazza, B. A. Patterson, S. Waldrop, W. Trigona, T.-M Fu, F. Kern, L. J. Picker, and R. A. Koup. Putative Immunodominant Human Imunodeficiency Virus-Specific CD8+ T Cell Responses Cannot Be Predicted by Major Histocompatibility Complex Class I Haplotype. J. Virol., 74:9144-9151, 2000. PubMed ID: 10982361. Show all entries for this paper.

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Displaying record number 52265

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords	epitope processing, immunodominance

Notes

• Epitope processing of three different HLA-A*0201 HIV epitopes was shown to use different pathways, which might influence patterns of immunodominance. .174 cells were used that lack TAP1 and TAP2 genes, as well as the LMP2 and LMP7 genes that encode the beta-subunits of the immunoproteasome. These genes could be added back through transfection to study processing.
• ILKEPVHGV was efficiently presented in TAP-1 and -2 transfected cells while VIYQYMDDL and SLYNTVATL were not. VIYQYMDDL was destroyed by the MB1 subunit of the protease, and could be expressed in the presence of the proteasome inhibitor lactacystin, but SLYNTVATL expression was not restored. SLYNTVATL expression was unaltered by lactacystin in a wild type cell line.

References

Sewell2002 Andrew K. Sewell, Bruce L. Booth, Jr., Vincenzo Cerundolo, Rodney E. Phillips, and David A. Price. Differential Processing of HLA A2-Restricted HIV Type 1 Cytotoxic T Lymphocyte Epitopes. Viral Immunol., 15(1):193-196, 2002. PubMed ID: 11952141. Show all entries for this paper.

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Displaying record number 52284

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IL-9
Species (MHC/HLA)	humanized mouse(A*02:01)
Immunogen	HIV-1 infected monocyte-derived
Experimental methods
Keywords

Notes

• Nonobese diabetic NOD-C.B-17 SCID mice were reconstituted with HLA-A*0201 positive human PBL and injected with HIV-1 infected monocyte-derived macrophages MDM in the basal ganglia to provide a mouse model of HIV-1 encephalitis.
• HLA-A*0201 CTL responses were detected by tetramer staining in the spleen in seven days, increased through day 14, and the numbers of productively infected were reduced >85% in the second week.

References

Poluektova2002 Larisa Y. Poluektova, David H. Munn, Yuri Persidsky, and Howard E. Gendelman. Generation of Cytotoxic T Cells Against Virus-Infected Human Brain Macrophages in a Murine Model of HIV-1 Encephalitis. J. Immunol., 168(8):3941-3949, 15 Apr 2002. PubMed ID: 11937550. Show all entries for this paper.

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Displaying record number 509

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART

Notes

• Administration of highly active antiretroviral therapy (HAART) reduced CD8+ cell frequency, and the CD8+ cells detected by tetramer staining were likely to be memory cells, indicating that persistently replicating viral populations are needed to maintain high frequencies of HIV-1 specific CTL.

References

Gray1999 C. M. Gray, J. Lawrence, J. M. Schapiro, J. D. Altman, M. A. Winters, M. Crompton, M. Loi, S. K. Kundu, M. M. Davis, and T. C. Merigan. Frequency of Class I HLA-Restricted Anti-HIV CD8+ T Cells in Individuals Receiving Highly Active Antiretroviral Therapy (HAART). J. Immunol., 162:1780-1788, 1999. PubMed ID: 9973442. Show all entries for this paper.

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Displaying record number 52291

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484 LAI)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	LR22
Subtype	B
Species (MHC/HLA)	mouse(A*02:01)
Immunogen	vaccine
Experimental methods
Keywords	binding affinity, vaccine-induced immune responses, immunodominance

Vaccine Details

Vaccine type	peptide
Vaccine strain	B clade LAI
Adjuvant	Incomplete Freund's Adjuvant (IFA), Montanide (ISA 720), P30, PLG

Notes

• The stability of peptide binding to HLA-A2.1 was determined for six HLA-A2.1 peptides included in this vaccine study -- ILKEPVHGV (RT), SLYNTVATL (p17), SLLNATDIAV (gp41) and LLWKGEGAV (RT) all bound with high affinity comparable to an influenza epitope reference (GILGFVFTL), while RGPGRAFVTI and VIYQYMDDL bound with a lower affinity (relative binding activity = 0.01).
• The four high-affinity peptides formed stable complexes with half-lives ranging between 8 and 32 hours, while the low affinity peptides had half-lives of less than an hour.
• HLA-A2.1 transgenic mice were immunized with the six HIV-1 peptides and P30, as a universal T-helper epitope, with IFA or Montanide or microspheres as adjuvants.
• All peptides except VIYQYMDDL induced a strong CTL response in Cr-release assays - stronger responses were observed when peptides were delivered alone, indicating immunodominance when the combination was used.

References

Peter2001 Katrin Peter, Ying Men, Giuseppe Pantaleo, Bruno Gander, and Giampietro Corradin. Induction of a Cytotoxic T-Cell Response to HIV-1 Proteins with Short Synthetic Peptides and Human Compatible Adjuvants. Vaccine, 19(30):4121-4129, 20 Jul 2001. PubMed ID: 11457536. Show all entries for this paper.

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Displaying record number 52292

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484 LAI)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	LR22
Subtype	B
Species (MHC/HLA)	mouse(A*02:01)
Immunogen	vaccine
Experimental methods
Keywords	vaccine-induced immune responses, immunodominance

Vaccine Details

Vaccine type	peptide
Vaccine strain	B clade LAI
Adjuvant	Incomplete Freund's Adjuvant (IFA), IL-12, P30

Notes

• When HIV-1 peptides were used to vaccinate HLA-A2.1 transgenic A2-Kb mice, strong responses to five peptides were observed when the peptides were given individually, but immunodominance limited the response to some of the peptides when they were given in combination Peter2001. IL-12 can counteract immunodominance in BALB/c mice, so it was given with the multiple epitope vaccination, and was instead found to specifically eliminate the HLA-A2.1-epitope CTL responses, but not Kb CTL responses. This was possibly a consequence of transient depletion of T-cells, B cells and macropahges in the spleen.

References

Peter2001 Katrin Peter, Ying Men, Giuseppe Pantaleo, Bruno Gander, and Giampietro Corradin. Induction of a Cytotoxic T-Cell Response to HIV-1 Proteins with Short Synthetic Peptides and Human Compatible Adjuvants. Vaccine, 19(30):4121-4129, 20 Jul 2001. PubMed ID: 11457536. Show all entries for this paper.

Peter2002 Katrin Peter, Michael J. Brunda, and Giampietro Corradin. IL-12 Administration Leads to a Transient Depletion of T Cells, B Cells, and APCs and Concomitant Abrogation of the HLA-A2.1-Restricted CTL Response in Transgenic Mice. J. Immunol., 169(1):63-67, 1 Jul 2002. PubMed ID: 12077229. Show all entries for this paper.

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Displaying record number 526

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(309-317)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

• This paper introduces the tetramer methodology which permits quantification of specific CTL based on expression of specific TCRs---HLA-A2 tetramers were prepared that can stain CTL lines specific for ILKEPVHGV and SLYNTVATL, and can quantify HIV-specific CD8+ cell lines in freshly isolated PBMCs.
• Three patients only stained the Gag epitope SLYNTVATL, one patient had the highest frequency of tetramer staining to the Pol epitope (0.77%), less to the Gag epitope (0.28%)
• The A2-Pol CD8+ clones were CD45RO positive and HLA-DR and CD38 negative, suggesting a memory rather than effector phenotype.

References

Altman1996 J. D. Altman, P. A. H. Moss, P. J. R. Goulder, D. H. Barouch, M. G. McHeyzer-Williams, J. I. Bell, A. J. McMichael, and M. M. Davis. Phenotypic analysis of antigen-specific T lymphocytes. Science, 274:94-6, 1996. Comments in Science 1998 Jun 19;280(5371):1821. PubMed ID: 8810254. Show all entries for this paper.

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Displaying record number 510

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

• HLA-tetrameric complexes were used in a cross-sectional study of 14 untreated HLA A*0201 positive individuals, revealing an inverse relationship between HIV Gag and Pol specific CTL effector cells (CTLe) and viral load.
• Inclusion of both the p17 SLYNTVATL and RT ILKEPVHGV epitopes gives a good representation of HLA A*0201-restricted activity.
• No correlation was observed between the CTLe and CD4 count or clearance rate of productively infected cells.

References

Menendez-Arias1998 L. Menendez-Arias, A. Mas, and E. Domingo. Cytotoxic T-Lymphocyte Responses to HIV-1 Reverse Transcriptase. Viral Immunol., 11:167-181, 1998. PubMed ID: 10189185. Show all entries for this paper.

Ogg1998 G. S. Ogg, X. Jin, S. Bonhoeffer, P. R. Dunbar, M. A. Nowak, S. Monard, J. P. Segal, Y. Cao, S. L. Rowland-Jones, V. Cerundolo, A. Hurley, M. Markowitz, D. D. Ho, D. F. Nixon, and A. J. McMichael. Quantitation of HIV-1-Specific Cytotoxic T Lymphocytes and Plasma Load of Viral RNA. Science, 279:2103-2106, 1998. PubMed ID: 9516110. Show all entries for this paper.

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Displaying record number 528

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	in vitro stimulation or selection
Experimental methods
Keywords	epitope processing

Notes

• HLA-A*02 heavy chain and β2-microglobulin expressed in E. coli were refolded in the presence of this peptide.
• The HLA-A*02-peptide complex elicited HLA-A2 peptide-specific CTL response in cells lacking HLA-A2.
• Suggests that preformed HLA-peptide complexes could provide an alternate to intracellular processing for immunogens.

References

Menendez-Arias1998 L. Menendez-Arias, A. Mas, and E. Domingo. Cytotoxic T-Lymphocyte Responses to HIV-1 Reverse Transcriptase. Viral Immunol., 11:167-181, 1998. PubMed ID: 10189185. Show all entries for this paper.

Walter1997 J. B. Walter, C. Brander, M. Mammen, D. N. Garboczi, S. A. Kalams, G. M. Whiteside, B. D. Walker, and H. N. Eisen. Stimulation of Human Cytotoxic T Cells with HIV-1-Derived Peptides Presented by Recombinant HLA-A2 Peptide Complexes. Int. Immunol., 9:451-459, 1997. HLA-A2 heavy chain and beta 2-microglobulin refolded in the presence of peptides became susceptible to lysis by HLA-A2-restricted cytotoxic T lymphocyte (CTL) clones specific for the peptides. Recombinant HLA-A2 peptide complexes covalently immobilized on microspheres stimulated the development of HLA-A2 peptide-specific CTL. PubMed ID: 9088983. Show all entries for this paper.

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Displaying record number 52346

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(309-317)
Epitope	ILKEPVHGV	Epitope Alignment
Subtype	B
Species (MHC/HLA)	transgenic mouse(A*02:01)
Immunogen	vaccine
Experimental methods
Keywords	binding affinity, vaccine-induced immune responses

Vaccine Details

Vaccine type	peptide
Vaccine component	RT
Adjuvant	Complete Freund's Adjuvant (CFA)

Notes

• Ten naturally occurring variants of the Nef epitope VLMWQFDSRL were tested for their affinity to HLA-A*0201 and for their ability to induce gamma-IFN and cytotoxic functions through vaccination of HLA-A*0201 transgenic mice.
• ILKEPVHGV could induce HLA-A*0201 vaccine responses, and was a positive control.

References

Boissonnas2002 Alexandre Boissonnas, Olivia Bonduelle, Ariane Antzack, Yu-Chun Lone, Cecile Gache, Patrice Debre, Brigitte Autran, and Behazine Combadiere. In Vivo Priming Of HIV-Specific CTLs Determines Selective Cross-Reactive Immune Responses Against Poorly Immunogenic HIV-Natural Variants. J. Immunol., 169(7):3694-3699, 1 Oct 2002. PubMed ID: 12244162. Show all entries for this paper.

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Displaying record number 52354

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(468-476)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	mouse(A*02:01)
Immunogen	vaccine
Experimental methods
Keywords	epitope processing, vaccine-induced immune responses, immunodominance

Vaccine Details

Vaccine type	DNA
Vaccine component	HIV-1

Notes

• C3H (H-2k) transgenic mice carrying a fused HLA-A*0201 alpha1 and alpha2 and H-2Dk alpha3 hybrid class I molecule were immunized using an epidermal gene gun with an ubiquitin expression library of 32 plasmids that spanned the HIV-1 genome. Ubiquitin targets the expressed HIV-1 peptides to the proteasome.
• A single immunization with the UB-HIV-1 library vaccine induced potent, stable and multivalent CTL responses against all library members.
• Immunodominant epitopes SLYNTVATL (Gag), ILKEPVHGV (Pol), RIQRGPGRAFVTIGK (Env) and AFHHVAREK (Nef) elicited strong CD8+/IFN- responses and stimulated CTL that were functional in a Cr-release assay and against wild type antigen.
• The presence of multiple plasmids HLA-A*0201-restricted CTL epitopes did not decrease CTL immunogenicity, and CTL responses to single peptide immunizations were comparable to responses based on mixtures of either 16 or 32 peptides.

References

Singh2002 Rana A. K. Singh, Lei Wu, and Michael A. Barry. Generation of Genome-Wide CD8 T Cell Responses in HLA-A*0201 Transgenic Mice by an HIV-1 Ubiquitin Expression Library Immunization Vaccine. J. Immunol., 168(1):379-391, 1 Jan 2002. PubMed ID: 11751984. Show all entries for this paper.

Sykes1999 Kathryn F. Sykes and Stephen Albert Johnston. Genetic live vaccines mimic the antigenicity but not pathogenicity of live viruses. DNA Cell Biol., 18(7):521-531, Jul 1999. PubMed ID: 10433551. Show all entries for this paper.

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Displaying record number 52439

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol
Epitope	ILKEPVHGV	Epitope Alignment
Subtype	A, B, C, D
Species (MHC/HLA)	human, macaque(A*02:01)
Immunogen	HIV-1 infection, vaccine
Experimental methods
Keywords	subtype comparisons, epitope processing, vaccine-induced immune responses, immunodominance

Vaccine Details

Vaccine type	DNA prime with modified vaccinia Ankara (MVA) boost
Vaccine strain	A clade
Vaccine component	p17 Gag, p24 Gag

Notes

• The HIV-1 subtype A focused vaccine HIVA contains p24 and p17, in a reversed order relative to the Gag polyprotein to prevent myristylation of p17, which could direct the protein to the cell membrane and inhibit efficient peptide processing and class I presentation, as well as a polyepitope string of conserved, often immunodominant epitopes that were selected to have particularly good cross-reactive potential for the A-clade epidemic in Nairobi, Kenya. A DNA and MVA prime-boost vaccination protocol using the HIVA antigen will be used in a phase III clinical trial in Kenya. This epitope is included in the polyepitope string Hanke2000.
• Multiple CD4+ or CD8+ T-cell vaccine-induced responses to peptide pools were detected using intracellular cytokine staining and IFNgamma Elispot assays after vaccination of 5 macaques. The response to the Mamu A*01 SIV p27 epitope p11C (CTPYDINQM), included in the polyepitope region, was not immunodominant in the Mamu A*01 vaccinated macaques, possibly because of processing limitations in context of the artificial polyepitope string Wee2002.

References

Hanke2000 Tomas Hanke and Andrew J. McMichael. Design and construction of an experimental HIV-1 vaccine for a year-2000 clinical trial in Kenya. Nat. Med., 6(9):951-955, Sep 2000. PubMed ID: 10973301. Show all entries for this paper.

Wee2002 Edmund G.-T. Wee, Sandip Patel, Andrew J. McMichael, and Tomáš Hanke. A DNA/MVA-Based Candidate Human Immunodeficiency Virus Vaccine for Kenya Induces Multi-Specific T Cell Responses in Rhesus Macaques. J. Gen. Virol., 83(Pt 1):75-80, Jan 2002. PubMed ID: 11752703. Show all entries for this paper.

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Displaying record number 511

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	vaccine
Experimental methods
Keywords

Vaccine Details

Vaccine type	vaccinia

Notes

• This epitope was shown to be processed and presented to appropriate CTL clones upon infection of human target cells with vaccinia virus Ankara (VVA) carrying 20 HIV-1 epitopes recognized by humans.

References

Hanke1998b T. Hanke, T. J. Blanchard, J. Schneider, G. S. Ogg, R. Tan, M. Becker, S. C. Gilbert, A. V. Hill, G. L. Smith, and A. McMichael. Immunogenicities of Intravenous and Intramuscular Administrations of Modified Vaccinia Virus Ankara-Based Multi-CTL Epitope Vaccine for Human Immunodeficiency Virus Type 1 in Mice. J. Gen. Virol., 79:83-90, 1998. PubMed ID: 9460927. Show all entries for this paper.

Hanke1998c T. Hanke, J. Schneider, S. G. Gilbert, A. V. S. Hill, and A. McMichael. DNA Multi-CTL Epitope Vaccines for HIV and Plasmodium falciparum: Immunogenicity in Mice. Vaccine, 16:426-435, 1998. PubMed ID: 9607066. Show all entries for this paper.

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Displaying record number 52577

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*02:01)
Immunogen	in vitro stimulation or selection
Experimental methods
Keywords	epitope processing, dendritic cells

Notes

• This study demonstrates that lipopeptides carrying epitopes can be taken up by human dendritic cells, processed using different pathways, and recognized by epitope-specific CD8+ T-cells originally derived from HIV+ individuals. The RT ILKEPVHGV peptide was embedded in a longer peptide fragment in the lipopeptide, and was internalized by endocytosis and processed in the cytosol by proteasomal cleavage by following an endosome-to-cytosol pathway for processing and presentation. Administration of epoxomycin, a proteasome inhibitor, completely abrogated epitope presentation to a CD8+ T-cell line, while monensin, an inhibitor of acid-dependent endosomal enzyme activity did not.
• In contrast to the RT epitope, dendritic cell presentation of the Nef epitope QVPLRPMTYK embedded in a longer peptide in a lipopeptide was not inhibited by epoxomycin, but was inhibited by monensin, indicative of endocytolitic epitope processing.

References

Andrieu2003 Muriel Andrieu, Jean-François Desoutter, Estelle Loing, Jésintha Gaston, Daniel Hanau, Jean-Gérard Guillet, and Anne Hosmalin. Two Human Immunodeficiency Virus Vaccinal Lipopeptides Follow Different Cross-Presentation Pathways in Human Dendritic Cells. J. Virol., 77(2):1564-1570, Jan 2003. PubMed ID: 12502869. Show all entries for this paper.

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Displaying record number 501

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords	acute/early infection

Notes

• Three individuals with highly focused HIV-specific CTL responses were studied during acute infection using tetramers -- high frequencies of HIV-1-specific CD8+ T cells were found prior to seroconversion, and a close temporal relationship between the number of circulating HIV-specific T cells and viral load.
• All three patients were B*2705, with HLA alleles: A1, A30/31, B*2705, B35; A1, A*0301, B7, B2705; and A*0201, A*0301, B2705, B39.
• ELISPOT was used to test a panel of CTL epitopes that had been defined earlier and were appropriate for the HLA haplotypes of the study subjects -- 3/3 subjects showed a dominant response to the B*2705 epitope KRWIILGGLNK.
• The subject with A*0201 had a moderately strong response to SLYNTVATL.
• Weak responses were observed to A*301-RLRPGGKKK, A*301-QVPLRPMTYK, and B7-TPGPGVRYPL in the subject who was HLA A1, A*0301, B7, B*2705.
• No acute response was detected to the following epitopes: A*201-ILKEPVHGV, A*301-KIRLRPGGK, A*301-AIFQSSMTK, A*301-TVYYGVPVWK, B35-EPIVGAETF, B35-HPDIVIYQY, B35-PPIPVGEIY, B35-NSSKVSQNY, B35-VPLRPMTY, B35-DPNPQEVVL.

References

Wilson2000 J. D. Wilson, G. S. Ogg, R. L. Allen, C. Davis, S. Shaunak, J. Downie, W. Dyer, C. Workman, S. Sullivan, A. J. McMichael, and S. L. Rowland-Jones. Direct Visualization of HIV-1-Specific Cytotoxic T Lymphocytes During Primary Infection. AIDS, 14:225-233, 2000. PubMed ID: 10716497. Show all entries for this paper.

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Displaying record number 1495

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484 LAI)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	P1
Subtype	B
Species (MHC/HLA)	human(A*02:01, A*02:05)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART

Notes

• A panel of 16 epitopes covering 15 class I alleles was tested in 14 HIV+ patients from an unselected Caucasian population treated with HAART, using tetramer staining or CD8+ cell IFNgamma production to measure responses.
• In general, during the first month of treatment viral load decreased and frequencies of HIV-specific CTL tripled and broadened -- eight new HIV specificities that were not previously detectable were newly detected, as were CMV specific CD8+ PBL -- but with continued viral suppression, HIV-specific responses diminished.
• Viral rebounds gave different patterns of response: increases or decreases in pre-existing response, new specificities, or no change.

References

Mollet2000 L. Mollet, T. S. Li, A. Samri, C. Tournay, R. Tubiana, V. Calvez, P. Debre, C. Katlama, and B. Autran. Dynamics of HIV-specific CD8+ T lymphocytes with changes in viral load. J. Immunol., 165(3):1692-704, 1 Aug 2000. URL: http://www.jimmunol.org/v165n3/1692/1692-abs-frame.html. PubMed ID: 10903781. Show all entries for this paper.

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Displaying record number 1427

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(464-472)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A*02:01, A2)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

• One of the 51 HIV-1 epitopes selected by Ferrari et al. as good candidate CTL epitopes for vaccines by virtue of being conserved and presented by common HLA alleles.

References

Ferrari2000 G. Ferrari, D. D. Kostyu, J. Cox, D. V. Dawson, J. Flores, K. J. Weinhold, and S. Osmanov. Identification of highly conserved and broadly cross-reactive HIV type 1 cytotoxic T lymphocyte epitopes as candidate immunogens for inclusion in Mycobacterium bovis BCG-vectored HIV vaccines. AIDS Res. Hum. Retroviruses, 16(14):1433-43, 20 Sep 2000. PubMed ID: 11018863. Show all entries for this paper.

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Displaying record number 535

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol( subtype B)
Epitope	ILKEPVHGV	Epitope Alignment
		Show epitope variants
Subtype	B
Species (MHC/HLA)	human(A*02:02, A2)
Immunogen	HIV-1 exposed seronegative
Experimental methods
Keywords	subtype comparisons

Notes

• HIV-specific CTL were found in exposed seronegative prostitutes from Nairobi -- these CTL may confer protection.
• Seroprevalence in this cohort is 90-95% and their HIV-1 exposure is among the highest in the world.
• Most isolated HIV strains are clade A in Nairobi, although clades C and D are also found -- B clade epitopes are often cross-reactive, however stronger responses are frequently observed using A or D clade versions of epitopes.
• This epitope is conserved among B and D clade viruses.
• Clade A version of the epitope, ILKDPVHGV, was preferentially recognized by CTL.
• Database note: First author "Rowland-Jones" is also found as "RowlandJones" on annotated papers in this database.

References

Rowland-Jones1998 S. L. Rowland-Jones, T. Dong, K. R. Fowke, J. Kimani, P. Krausa, H. Newell, T. Blanchard, K. Ariyoshi, J. Oyugi, E. Ngugi, J. Bwayo, K. S. MacDonald, A. J. McMichael, and F. A. Plummer. Cytotoxic T cell responses to multiple conserved HIV epitopes in HIV-resistant prostitutes in Nairobi. J. Clin. Invest., 102(9):1758-65, 1 Nov 1998. PubMed ID: 9802890. Show all entries for this paper.

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Displaying record number 55015

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding
Keywords	binding affinity

Notes

• CTL responses were tested for both HIV-1 and EBV derived epitopes restricted by HLA-A, -B and -C alleles. HLA-B alleles more frequently induce detectable responses and that the responses are generally of greater magnitude than those for HLA-A and -C alleles.
• The magnitude and frequency of CTL recognition were related to each other and that TCR avidity for HLA/peptide complexes is a more important determinant for magnitude of response than peptide binding affinity to HLA.
• EBV response patterns were not significantly altered by HIV coinfection.
• Epitope ILKEPVHGV elicited a magnitude of response of 110 SFC with a functional avidity of 0.01nM.

References

Bihl2006 Florian Bihl, Nicole Frahm, Loriana Di Giammarino, John Sidney, Mina John, Karina Yusim, Tonia Woodberry, Kaori Sango, Hannah S. Hewitt, Leah Henry, Caitlyn H. Linde, John V. Chisholm, III, Tauheed M. Zaman, Eunice Pae, Simon Mallal, Bruce D Walker, Alessandro Sette, Bette T. Korber, David Heckerman, and Christian Brander. Impact of HLA-B Alleles, Epitope Binding Affinity, Functional Avidity, and Viral Coinfection on the Immunodominance of Virus-Specific CTL Responses. J. Immunol., 176(7):4094-4101, 1 Apr 2006. PubMed ID: 16547245. Show all entries for this paper.

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Displaying record number 506

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
		Show epitope variants
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods
Keywords	subtype comparisons, TCR usage

Notes

• TCR usage in CTL specific for this epitope was examined in three patients and identical Vβ6.1 and Valpha2.5 gene segments were used and two of the patients had very similar complementarity-determining regions -- clonal expansion of RT-HIV-specific CTL can contribute to the skewed TCR repertoire in HIV-1 infected patients.
• CTL clones from all three patients showed similar sensitivity to mutation in the epitope, ilkepvhEv was well recognized (the sequence from SF2), ilkDpvhgv was not (the common A clade form)

References

Kolowos1999 W. Kolowos, M. Schmitt, M. Herrman, E. Harrer, P. Low, J. R. Kalden, and T. Harrer. Biased TCR Repertoire in HIV-1-Infected Patients Due to Clonal Expansion of HIV-1-Reverse Transcriptase-Specific CTL Clones. J. Immunol., 162:7525-7533, 1999. PubMed ID: 10358208. Show all entries for this paper.

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Displaying record number 512

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

• Nef down-regulates MHC class I molecules, which inhibits CTL killing of HIV-infected targets.
• The anti-RT CTL clone killed Nef- cells less efficiently than anti-gag clones, correlated with the reduced expression of RT.

References

Collins1998 K. L. Collins, B. K. Chen, S. A. Kalams, B. D. Walker, and D. Baltimore. HIV-1 Nef Protein Protects Infected Primary Cells against Killing by Cytotoxic T Lymphocytes. Nature, 391:397-401, 1998. PubMed ID: 9450757. Show all entries for this paper.

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Displaying record number 513

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484 LAI)
Epitope	ILKEPVHGV	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods
Keywords	dendritic cells

Notes

• The capacity of dendritic cells to process and present antigen and stimulate anti-HIV-1 CTL memory responses was studied.

References

Fan1997 Z. Fan, X. L. Huang, L. Zheng, C. Wilson, L. Borowski, J. Liebmann, P. Gupta, J. Margolick, and C. Rinaldo. Cultured Blood Dendritic Cells Retain HIV-1 Antigen-Presenting Capacity for Memory CTL During Progressive HIV-1 Infection. J. Immunol., 159:4973-4982, 1997. PubMed ID: 9366424. Show all entries for this paper.

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Displaying record number 514

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(464-472)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods
Keywords	dendritic cells

Notes

• Allogeneic dendritic cells (DCs) were obtained from HLA-identical siblings, pulsed with rgp160 MN or A2-restricted HIV-1 epitope peptides, and infused monthly into six HIV-infected patients.
• 1/6 showed increased env-specific CTL and increased lymphoproliferative responses, 2/6 showed increase only in proliferative responses, and 3/6 showed no change -- pulsed DCs were well tolerated.
• ILKEPVHGV is a conserved HLA-A2 epitope included in this study -- 5/6 patients had this sequence as their HIV direct sequence, and these had a detectable CTL response-- one person carried the form ILREPVHGV and had no detectable CTL.

References

Kundu1998 S. K. Kundu, E. Engleman, C. Benike, M. H. Shapero, M. Dupuis, W. C. van Schooten, M. Eibl, and T. C. Merigan. A Pilot Clinical Trial of HIV Antigen-Pulsed Allogeneic and Autologous Dendritic Cell Therapy in HIV-Infected Patients. AIDS Res. Hum. Retroviruses, 14:551-560, 1998. PubMed ID: 9591709. Show all entries for this paper.

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Displaying record number 515

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
		Show epitope variants
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

• CTL clones recognize naturally processed peptide -- peptide abundance corresponded to level of CTL killing.

References

Menendez-Arias1998 L. Menendez-Arias, A. Mas, and E. Domingo. Cytotoxic T-Lymphocyte Responses to HIV-1 Reverse Transcriptase. Viral Immunol., 11:167-181, 1998. PubMed ID: 10189185. Show all entries for this paper.

Tsomides1994 T. J. Tsomides, A. Aldovini, R. P. Johnson, B. D. Walker, R. A. Young, and H. N. Eisen. Naturally Processed Viral Peptides Recognized by Cytotoxic T Lymphocytes on Cells Chronically Infected by Human Immunodeficiency Virus Type 1. J. Exp. Med., 180:1283-1293, 1994. Naturally processed peptides can be purified from trifluoroacetic acid lysates of HIV-1 infected cells. A gag and RT epitope were compared; both synthetic peptides are optimally active in CTL assays. The naturally processed gag peptide was more abundant than the RT peptide in HIV-1 infected HLA-A2 positive cells, and the gag specific CTL more effective, suggesting surface density of peptides may influence efficiency of CTL killing. PubMed ID: 7523570. Show all entries for this paper.

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Displaying record number 517

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
		Show epitope variants
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 exposed seronegative
Experimental methods
Keywords	subtype comparisons, HIV exposed persistently seronegative (HEPS)

Notes

• A CTL response was found in exposed but uninfected prostitutes from Nairobi using previously-defined B clade epitopes that tended to be conserved in A and D clades -- such cross-reactivity could protect against both A and D and confer protection in Nairobi where both subtypes are circulating.
• The A subtype consensus is ILKDPVHGV.
• The D subtype consensus is identical to the epitope ILKEPVHGV.
• Database note: First author "RowlandJones" is also found as "Rowland-Jones" on annotated papers in this database.

References

RowlandJones1998b S. Rowland-Jones, T. Dong, P. Krausa, J. Sutton, H. Newell, K. Ariyoshi, F. Gotch, S. Sabally, T. Corrah, J. Kimani, K. MacDonald, F. Plummer, J. Ndinya-Achola, H. Whittle, and A. McMichael. The Role of Cytotoxic T Cells in HIV Infection. Dev. Biol. Stand., 92:209-214, 1998. In this paper CTL response to previously defined conserved epitopes was found in exposed but uninfected prostitutes in Nairobi. Subtypes A and D are circulating in this regions, and the reactive epitopes tended to be conserved. Similarly previous studies in the Gambia showed that exposed but uninfected prostitutes tended to have B35 presented CTL epitopes conserved between HIV-1 and HIV-2. It was suggested that what was special about B35 is simply that it presents epitopes found both in HIV-1 and HIV-2. PubMed ID: 9554277. Show all entries for this paper.

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Displaying record number 518

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
		Show epitope variants
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods
Keywords	subtype comparisons

Notes

• The consensus peptides of B and D clade viruses and some As have the sequence ILKEPVHGV.
• The consensus peptide of a subset of A clade viruses, ILKDPVHGV, is not cross-reactive.

References

Cao1997a H. Cao, P. Kanki, J. L. Sankale, A. Dieng-Sarr, Gail P. Mazzara, S. Kalams, B. Korber, S. M'Boup, and B. D. Walker. CTL Cross-Reactivity among Different HIV-1 Clades: Implications for Vaccine Development. J. Virol., 71:8615-8623, 1997. PubMed ID: 9343219. Show all entries for this paper.

Menendez-Arias1998 L. Menendez-Arias, A. Mas, and E. Domingo. Cytotoxic T-Lymphocyte Responses to HIV-1 Reverse Transcriptase. Viral Immunol., 11:167-181, 1998. PubMed ID: 10189185. Show all entries for this paper.

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Displaying record number 523

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

• CD4+ cell lines acutely infected with HIV were studied to determine their susceptibility to lysis by CTL.
• Clones specific for RT lysed HIV-1 infected cells at lower levels than Env or Gag specific clones.
• The distinction was thought to be due to lower expression of RT relative to Env and Gag.
• CTL can lyse infected cells early after infection, possibly prior to viral production.

References

Menendez-Arias1998 L. Menendez-Arias, A. Mas, and E. Domingo. Cytotoxic T-Lymphocyte Responses to HIV-1 Reverse Transcriptase. Viral Immunol., 11:167-181, 1998. PubMed ID: 10189185. Show all entries for this paper.

Yang1996 O. O. Yang, S. A. Kalams, M. Rosenzweig, A. Trocha, N. Jones, M. Koziel, B. D. Walker, and R. P. Johnson. Efficient Lysis of Human Immunodeficiency Virus Type 1-Infected Cells by Cytotoxic T Lymphocytes. J. Virol., 70:5799-5806, 1996. PubMed ID: 8709196. Show all entries for this paper.

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Displaying record number 524

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods	CTL suppression of replication
Keywords

Notes

• CTL inhibit HIV-1 replication at effector cell concentrations comparable to those found in vivo.
• CTL produced HIV-1-suppressive soluble factors -- MIP-1α, MIP-1β, RANTES, after antigen-specific activation.
• CTL suppress HIV replication more efficiently in HLA-matched cells.

References

Yang1997 O. O. Yang, S. A. Kalams, A. Trocha, H. Cao, A. Luster, R. P. Johnson, and B. D. Walker. Suppression of Human Immunodeficiency Virus Type 1 Replication by CD8+ Cells: Evidence for HLA Class I-Restricted Triggering of Cytolytic and Noncytolytic Mechanisms. J. Virol., 71:3120-3128, 1997. Although CD8+ lymphocytes in human immunodeficiency virus type 1 (HIV-1)-infected individuals have been demonstrated to suppress viral replication, the mechanisms of inhibition have not been defined precisely. A large body of evidence indicates that these cells act via soluble inhibitory factors, but the potential role of HLA class I-restricted cytolysis has remained controversial. Here we demonstrate that HIV-1-specific cytotoxic T lymphocytes (CTL) mediate antiviral suppression by both cytolytic and noncytolytic mechanisms. The predominant mechanism requires direct contact of CTL with the infected cells, is HLA class I restricted, and can achieve complete elimination of detectable virus in infected cell cultures. Inhibition occurs even at high multiplicities of infection or at ratios of CTL to CD4 cells as low as 1:1,000. The other mechanism is mediated by soluble inhibitory factors which are triggered in an antigen-specific and HLA-restricted fashion but then act without HLA restriction. PubMed ID: 9060675. Show all entries for this paper.

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Displaying record number 525

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(309-317)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods
Keywords	TCR usage

Notes

• Two clones were obtained with different TCR usage, V_beta1 and V_beta21.

References

Menendez-Arias1998 L. Menendez-Arias, A. Mas, and E. Domingo. Cytotoxic T-Lymphocyte Responses to HIV-1 Reverse Transcriptase. Viral Immunol., 11:167-181, 1998. PubMed ID: 10189185. Show all entries for this paper.

Moss1995 P. A. H. Moss, S. L. Rowland-Jones, P. M. Frodsham, S. McAdam, P. Giangrande, A. McMichael, and J. I. Bell. Persistent High Frequency of Human Immunodeficiency Virus-Specific Cytotoxic T Cells in Peripheral Blood of Infected Donors. Proc. Natl. Acad. Sci. U.S.A., 92:5773-5777, 1995. PubMed ID: 7597028. Show all entries for this paper.

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Displaying record number 527

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

• Cervical CTL clones from an HIV-infected woman recognized this epitope.

References

Menendez-Arias1998 L. Menendez-Arias, A. Mas, and E. Domingo. Cytotoxic T-Lymphocyte Responses to HIV-1 Reverse Transcriptase. Viral Immunol., 11:167-181, 1998. PubMed ID: 10189185. Show all entries for this paper.

Musey1997 L. Musey, Y. Hu, L. Eckert, M. Christensen, T. Karchmer, and M. J. McElrath. HIV-1 Induces Cytotoxic T Lymphocytes in the Cervix of Infected Women. J. Exp. Med., 185:293-303, 1997. Mononuclear cells in cytobrush specimens from the cervical samples were stimulated with antigen. Eight women with CD4 positive counts $>=$ 500 cells/$\mu$l had HIV-1-specific CTL, but only 4/11 with counts $<$ 500 cells/$\mu$l had HIV-1-specific CTL responses. PubMed ID: 9016878. Show all entries for this paper.

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Displaying record number 529

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484 LAI)
Epitope	ILKEPVHGV	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

• Precise identification of the nonamer that binds to A*02.

References

Menendez-Arias1998 L. Menendez-Arias, A. Mas, and E. Domingo. Cytotoxic T-Lymphocyte Responses to HIV-1 Reverse Transcriptase. Viral Immunol., 11:167-181, 1998. PubMed ID: 10189185. Show all entries for this paper.

Tsomides1991 T. J. Tsomides, B. D. Walker, and H. N. Eisen. An Optimal Viral Peptide Recognized by CD8+ T Cells Binds Very Tightly to the Restricting Class I Major Histocompatibility Complex Protein on Intact Cells but Not to the Purified Class I Protein. Proc. Natl. Acad. Sci. U.S.A., 88:11276-11280, 1991. PubMed ID: 1722325. Show all entries for this paper.

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Displaying record number 530

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484 LAI)
Epitope	ILKEPVHGV	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A2)
Immunogen	peptide-HLA interaction
Experimental methods
Keywords

Notes

• Promotes assembly of HLA*0-A2 molecules in T2 cell lysates.

References

Connan1994 F. Connan, F. Hlavac, J. Hoebeke, J. G. Guillet, and J. Choppin. A Simple Assay for Detection of Peptides Promoting the Assembly of HLA Class I Molecules. Eur. J. Immunol., 24:777-780, 1994. Peptides from influenza and HIV-1 were tested for their ability to promote the assembly of HLA-A2 and HLA-B51 molecules in T2 cell lysates. HIV Pol 476-484 allowed significant assembly of HLA-A2, and is a target for CTL. Nef peptide 186-194 produced significant assembly of HLA-B51. A hydrophobic anchor residue (V, L, I) at position 9 could occupy pocket F, and a hydrophobic residue (V, L) at position 3 or 4 may anchor to hydrophobic pocket D of HLA-B51. Proline at position 2 increases HLA-B51 anchoring. PubMed ID: 8125145. Show all entries for this paper.

Menendez-Arias1998 L. Menendez-Arias, A. Mas, and E. Domingo. Cytotoxic T-Lymphocyte Responses to HIV-1 Reverse Transcriptase. Viral Immunol., 11:167-181, 1998. PubMed ID: 10189185. Show all entries for this paper.

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Displaying record number 531

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(510-518)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	in vitro stimulation or selection
Experimental methods
Keywords

Notes

• Studied in the context of HLA-A2 peptide binding.

References

Parker1992 K. C. Parker, M. A. Bednarek, L. K. Hull, U. Utz, B. Cunningham H. J. Zweerink, W. E. Biddison, and J. E. Coligan. Sequence Motifs Important for Peptide Binding to the Human MHC Class I Molecule, HLA-A2. J. Immunol., 149, 1992. PubMed ID: 1331239. Show all entries for this paper.

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Displaying record number 533

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

• CTL specific responses were measured over a 1.3 to 1.5 year period in members of the Sydney Blood Bank Cohort (SBBC) who had been infected with a natural attenuated strain of HIV-1 which was Nef-defective.
• Some of these patients had prolonged high levels of CTL effector and memory cells despite low viral load.

References

Dyer1999 W. B. Dyer, G. S. Ogg, M. A. Demoitie, X. Jin, A. F. Geczy, S. L. Rowland-Jones, A. J. McMichael, D. F. Nixon, and J. S. Sullivan. Strong Human Immunodeficiency Virus (HIV)-Specific Cytotoxic T-Lymphocyte Activity in Sydney Blood Bank Cohort Patients Infected with nef-Defective HIV Type 1. J. Virol., 73:436-443, 1999. PubMed ID: 9847349. Show all entries for this paper.

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Displaying record number 534

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	in vitro stimulation or selection
Experimental methods
Keywords	dendritic cells

Notes

• This study compares the ability of macrophages and dendritic cells to stimulate primary responses in CD8+ lymphocytes isolated from HLA-appropriate HIV-uninfected donors using peptide-pulsed APC -- the dendritic cells performed better as APC for the stimulation of primary responses.
• Strong CTL responses were elicited by the epitopes DRFYKTLRA and GEIYKRWII when presented by either immature or mature dendritic cells -- macrophages were not able to prime a CTL response against DRFYKTLRA.
• A weak response to KLTPLCVSL was stimulated using macrophages as the APC.
• No detectable response was observed for the following previously-defined HIV epitopes: KIRLRPGGK, ILKEPVHGV, IRLRPGGK, GPKVKQWPL.

References

Zarling1999 A. L. Zarling, J. G. Johnson, R. W. Hoffman, and D. R. Lee. Induction of Primary Human CD8+ T Lymphocyte Responses In Vitro Using Dendritic Cells. J. Immunol., 162:5197-5204, 1999. PubMed ID: 10227993. Show all entries for this paper.

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Displaying record number 537

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(480-)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	(A2)
Immunogen	computer prediction
Experimental methods	Other
Keywords	subtype comparisons, computational epitope prediction

Notes

• This study uses EpiMatrix for T cell epitope prediction to identify possible HLA-B27 and A-2 CTL epitopes in HIV.
• Based on EpiMatrix predictions, 28 peptides were synthesized and tested using T2 binding assays for potential HLA A2 or B27 binding, and 12 of these were shown to bind to the predicted HLA molecule.
• Two of these 12 peptides had been previously identified as CTL epitopes: HLA-B27 KRWILGLNK and HLA-A2 ILKEPVHGV.
• This sequence is not conserved between clades, but is found only in a small number of B clade isolates.

References

Schafer1998 J. R. Schafer, B. M. Jesdale, J. A. George, N. M. Kouttab, and A. S. De Groot. Prediction of Well-Conserved HIV-1 Ligands Using a Matrix-Based Algorithm, EpiMatrix. Vaccine, 16:1880-1884, 1998. PubMed ID: 9795396. Show all entries for this paper.

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Displaying record number 1313

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	RT IV9
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods
Keywords	binding affinity, supertype, computational epitope prediction, HLA cross-presentation

Notes

• HIV was scanned for all peptides which carried the A2-supermotif pattern conserved in more than 50% of B clade sequences -- 233 peptides met this criteria, and 30 of these bound to HLA-A*0201 -- 20/30 bound to at least 3/5 of HLA-A2 supertype alleles tested.
• Three additional previously described HLA-A2 epitopes were added to the set of 20, and 18/22 chronically infected HLA-A2 individuals had CTL that recognized at least one of the 23 peptides (median of 2 and maximum of 6), while 6/12 acute infected individuals recognized at least 1 (median of 1 and maximum of 2)
• This peptide binds to four HLA-A2 supertype alleles: A*0201, A*0202, A*0206 (highest affinity) and A*6802.
• RT IV9 was recognized in 7/22 patients with chronic HIV-1 infection.
• 1/13 patients with acute HIV-1 infection recognized RT IV9.

References

Altfeld2001 M. A. Altfeld, B. Livingston, N. Reshamwala, P. T. Nguyen, M. M. Addo, A. Shea, M. Newman, J. Fikes, J. Sidney, P. Wentworth, R. Chesnut, R. L. Eldridge, E. S. Rosenberg, G. K. Robbins, C. Brander, P. E. Sax, S. Boswell, T. Flynn, S. Buchbinder, P. J. Goulder, B. D. Walker, A. Sette, and S. A. Kalams. Identification of novel HLA-A2-restricted human immunodeficiency virus type 1-specific cytotoxic T-lymphocyte epitopes predicted by the HLA-A2 supertype peptide-binding motif. J. Virol., 75(3):1301-11, Feb 2001. URL: http://jvi.asm.org/cgi/content/full/75/3/1301. PubMed ID: 11152503. Show all entries for this paper.

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Displaying record number 1346

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(309-317)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	RT2
Species (MHC/HLA)	human, transgenic mouse(A2)
Immunogen	in vitro stimulation or selection, vaccine
Experimental methods
Keywords	epitope processing

Vaccine Details

Vaccine type	HIV-1 peptide in filamentous bacteriophage major coat protein
Vaccine component	RT

Notes

• Phage display of the CTL epitope, ILKEPVHGV coupled with T helper epitope KDSWTVNDIQKLVGK, elicited specific CTL responses in vitro in PBMC from HIV negative individuals and in vivo in immunization of HLA-A2 transgenic mice.
• Bacteriophage presentation of peptides is generally used for stimulation of antibodies, and this novel discovery of CTL epitope processing and presentation suggests new possibilities for these vectors.

References

DeBerardinis2000 P. De Berardinis, R. Sartorius, C. Fanutti, R. N. Perham, G. Del Pozzo, and J. Guardiola. Phage Display of Peptide Epitopes from HIV-1 Elicits Strong Cytolytic Responses. Nat. Biotechnol., 18(8):873-876, Aug 2000. PubMed ID: 10932158. Show all entries for this paper.

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Displaying record number 1369

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	ILK
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART, supervised treatment interruptions (STI), immunodominance, acute/early infection

Notes

• Patients who started therapy at acute HIV-1 infection (three with sustained therapy, two with limited therapy upon early infection) had strong HIV specific CD4 proliferative responses and were able to maintain a CTL response even with undetectable viral load -- three patients that had delayed initiation of HAART had no HIV specific CD4 proliferative responses and lost their CTL responses when HAART was eventually given and their viral loads became undetectable.
• One of the 2/8 HLA-A2+ study subjects recognized this CTL epitope.
• Patient SC9 (HLA A1/2, B8/13, Cw0/0701, DR2/11, DQ6/7) had a CTL response against epitopes FLKEKGGL, ILKEPVHGV, SQRRQDILDLWIYHTQGYFPDWQNY, and GEIYKRWII peptides and all responses declined during therapy initiated at day 390 but were restored when therapy become intermittent.

References

Oxenius2000b A. Oxenius, D. A. Price, P. J. Easterbrook, C. A. O'Callaghan, A. D. Kelleher, J. A. Whelan, G. Sontag, A. K. Sewell, and R. E. Phillips. Early highly active antiretroviral therapy for acute HIV-1 infection preserves immune function of CD8+ and CD4+ T lymphocytes. Proc. Natl. Acad. Sci. U.S.A., 97(7):3382-7, 28 Mar 2000. URL: http://www.pnas.org/cgi/content/full/97/7/3382. PubMed ID: 10737796. Show all entries for this paper.

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Displaying record number 1407

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

• HLA tetramers to six epitopes were used to study HLA-A2, B8 and B57 CTL in 54 patients -- HIV-specific tetramer positive cells were inversely correlated with viral load in patients with high CD4, but in patients with CD4 T-cells below 400 high tetramer frequencies were found despite high viral load.
• Most patients have high levels of HIV-specific T-cell expansions, but many of these cells aren't functional.
• In 15 of the patients, the proportion of IFN gamma producing tetramer cells correlated with AIDS-free survival.

References

Kostense2001 S. Kostense, G. S. Ogg, E. H. Manting, G. Gillespie, J. Joling, K. Vandenberghe, E. Z. Veenhof, D. van Baarle, S. Jurriaans, M. R. Klein, and F. Miedema. High viral burden in the presence of major HIV-specific CD8(+) T cell expansions: evidence for impaired CTL effector function. Eur. J. Immunol., 31(3):677-86, Mar 2001. PubMed ID: 11241270. Show all entries for this paper.

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Displaying record number 1483

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART, immunodominance

Notes

• CTL responses were studied by tetramer staining in 41 patients with combination therapy -- activated CD8+ T-cells decline as the viral load drops in response to therapy, but the overall level of antigen-specific cells capable of differentiating into effectors stays constant and new epitopes may be recognized.
• 6/10 A*0201+ individuals had HIV-specific tetramer staining cells, and 5 of these declined upon successful therapy.
• 3/10 A*0201+ individuals with chronic HIV-1 infection recognized this epitope.
• Prior to therapy, the mean percentage of CD8+ cells that recognized the immunodominant epitope SLYNTVATL was six-fold greater than the percentage recognizing the epitope ILKEPVHGV.

References

Seth2001 A. Seth, J. Markee, A. Hoering, A. Sevin, D. E. Sabath, J. E. Schmitz, M. J. Kuroda, M. A. Lifton, M. S. Hirsch, A. C. Collier, N. L. Letvin, and M. J. McElrath. Alterations in T cell phenotype and human immunodeficiency virus type 1-specific cytotoxicity after potent antiretroviral therapy. J. Infect. Dis., 183(5):722-9, 1 Mar 2001. PubMed ID: 11181148. Show all entries for this paper.

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Displaying record number 1520

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484 SF2)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART, acute/early infection

Notes

• Therapy provided during acute infection resulted in a narrower CTL response, stronger T help response, and a less diverse viral population than was seen in individuals treated during chronic infection.
• The breadth and specificity of the response was determined using ELISPOT by studying 19 individuals with pre-seroconversion therapy (Group 1), 11 individuals with primary infection but post-seroconversion therapy (Group 2), and 10 individuals who responded to HAART given during chronic infection (Group 3), using 259 overlapping peptides spanning p17, p24, RT, gp41, gp120 and Nef.
• Previously described and newly defined optimal epitopes were tested for CTL response.
• Number of HLA-A2+ individuals that had a CTL response to this epitope broken down by group: 1/10 group 1, 0/6 group 2, and 3/4 group 3.

References

Altfeld2001b M. Altfeld, E. S. Rosenberg, R. Shankarappa, J. S. Mukherjee, F. M. Hecht, R. L. Eldridge, M. M. Addo, S. H. Poon, M. N. Phillips, G. K. Robbins, P. E. Sax, S. Boswell, J. O. Kahn, C. Brander, P. J. Goulder, J. A. Levy, J. I. Mullins, and B. D. Walker. Cellular immune responses and viral diversity in individuals treated during acute and early HIV-1 infection. J. Exp. Med., 193(2):169-80, 15 Jan 2001. URL: http://www.jem.org/cgi/content/full/193/2/169. PubMed ID: 11148221. Show all entries for this paper.

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Displaying record number 52177

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(476-484 LAI)
Epitope	ILKEPVHGV	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART, epitope processing

Notes

• Ritonavir (RTV) inhibits chymotryptic activity in the 20S proteasome in vitro, as does Saquinavir (SQV) to a lesser extent; Indinavir (IDV) does not. Thus there is concern protease inhibitors may adversely affect CTL epitope processing, but this paper indicates that processing is not inhibited at therapeutically relevant concentrations of RTV when the proteasome is functioning in in an intracellular context.
• RTV did not alter the presentation two RT A2 epitopes processed by distinct pathways: ILKEPVHGV, generated by the constitutive proteasome containing the MB1 beta subunit, and VIYQYMDDL which is dependent on IFNgamma induction of LMP7 which replaces MB1 in the immunoproteasome, and is destroyed by MB1 in the constitutive proteasome.
• RTV did not inhibit the processing and assembly of HLA-B35 or -A2, which are assembled with a rapid and moderate time course, respectively, or of HLA-A3, -B27 and -B39.

References

Kelleher2001a A. D. Kelleher, B. L. Booth, Jr., A. K. Sewell, A. Oxenius, V. Cerundolo, A. J. McMichael, R. E. Phillips, and D. A. Price. Effects of Retroviral Protease Inhibitors on Proteasome Function and Processing of HIV-Derived MHC Class I-Restricted Cytotoxic T Lymphocyte Epitopes. AIDS Res. Hum. Retroviruses, 17(11):1063-1066, 20 Jul 2001. PubMed ID: 11485623. Show all entries for this paper.

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Displaying record number 52237

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484 NL43)
Epitope	ILKEPVHGV	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods
Keywords	class I down-regulation by Nef

Notes

• Nef down-modulates class I protein expression, and this study demonstrates directly that Nef-deleted HIV-1 NL-43 can be more effectively killed in vitro than NL-43 with an intact Nef. The effect was shown to be specific for class I presentation of epitopes, and unlike Nef, deleting Vpr did not alter CTL susceptibility of NL-43 infected cells. The CTL clone 68A62, specific for the class I A2 presented ILKEPVHGV epitope, was one of four used in this study.

References

Yang2002 Xinzhen Yang, Juliette Lee, Erin M. Mahony, Peter D. Kwong, Richard Wyatt, and Joseph Sodroski. Highly Stable Trimers Formed by Human Immunodeficiency Virus Type 1 Envelope Glycoproteins Fused with the Trimeric Motif of T4 Bacteriophage Fibritin. J. Virol., 76(9):4634-4642, 1 May 2002. PubMed ID: 11932429. Show all entries for this paper.

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Displaying record number 52286

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484 BRU)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Patient MHC/HLA	A2
Experimental methods
Keywords	epitope processing

Notes

• The antigen presentation of two A2-restricted epitopes was compared, SLYNTVATL (p17) and ILKEPVHGV (RT). HIV-1 infected cells were more sensitive to lysis by SLYNTVATL-specific CTL than by ILKEPVHGV-specific CTL, because of a higher density of SLYNTVATL-A2 resulting from differences in processing.
• Incubation with a T1-cell proteolytic extract showed that by four hours, 25% of a p17 peptide had a C-term Leu-85 and were SLYNTVATL-precursors, while ILKEPVHGV-precursors were far less frequent (6.8%) even with four times more proteolytic extract after 30 hours.
• p17 was preferentially cleaved between Leu85 and Tyr86, while appropriate Val484 and Tyr485 cleavage was minor for RT.
• In a competition experiment, RSLYNTVATL bound TAP 3.7-fold more efficiently than RT peptides.
• No difference in CTL avidity was detected in six patients with HLA-A2-restricted responses to these epitopes.
• No significant difference in HLA-A2 binding of to p17 or RT epitopes was observed.

References

Cohen2002 W. M. Cohen, A. Bianco, F. Connan, L. Camoin, M. Dalod, G. Lauvau, E. Ferriés, B. Culmann-Penciolelli, P. M. van Endert, J. P. Briand, J. Choppin, and J. G. Guillet. Study of Antigen-Processing Steps Reveals Preferences Explaining Differential Biological Outcomes of Two HLA-A2-Restricted Immunodominant Epitopes from Human Immunodeficiency Virus Type 1. J. Virol., 76(20):10219-10225, Oct 2002. PubMed ID: 12239297. Show all entries for this paper.

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Displaying record number 52305

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	p9
Species (MHC/HLA)	mouse(A2)
Immunogen	vaccine
Experimental methods
Keywords

Vaccine Details

Vaccine type	peptide
Adjuvant	Complete Freund's Adjuvant (CFA)

Notes

• BALB/c mice immunized with the p9 peptide, ILKEPVHGV, elicited specific lymphocyte proliferation activity.
• Exposure of lymphocytes from HIV-negative, HLA-A2 positive people to p9-RNA stimulated lymphocyte proliferation activity to p9. Anti-p9 CTL activity in human lymphocytes incubated with RNA extracted from lymphoid organs of p9-vaccinated mice could be more intensely stimulated.
• This murine RNA also mediated RNA-dependent protein kinase (PKR) and NFkappaB activation in the human lymphocytes, which may be driving the enhanced CTL stimulation in the human cells.

References

DeLucca2002 Fernando L. De Lucca, Valeria S. F. Sales, Liliana R. Souza, and Maria Angelica E. Watanabe. Evidence for the Involvement of the RNA-Dependent Protein Kinase (PKR) in the Induction of Human Cytotoxic T Lymphocytes against a Synthetic Peptide of HIV-1 by Regulatory RNA. Mol Cell Biochem, 238(1-2):19-26, Sep 2002. PubMed ID: 12349906. Show all entries for this paper.

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Displaying record number 52315

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	ILK
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART, supervised treatment interruptions (STI)

Notes

• Using previously defined epitopes Oxenius2000b,Oxenius2001b in an IFNgamma Elispot assay, 13 chronically HIV-1 infected patients were studied over a period including therapy with standard treatment interruptions (STI).
• STIs induced increased recognition of CTL epitopes, but there was no correlation between CTL responses with viral rebound rates, plateau viral loads, or clearance rates.

References

Oxenius2002b Annette Oxenius, Angela R. McLean, Marek Fischer, David A. Price, Sarah J. Dawson, Roland Hafner, Christine Schneider, Helen Joller, Bernard Hirschel, Rodney E. Phillips, Rainer Weber, Huldrych F. Günthard, and Swiss HIV Cohort Study Group. Human Immunodeficiency Virus-Specific CD8+ T-Cell Responses Do Not Predict Viral Growth and Clearance Rates During Structured Intermittent Antiretroviral Therapy. J. Virol., 76(20):10169-10176, Oct 2002. PubMed ID: 12239291. Show all entries for this paper.

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Displaying record number 52339

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	p51(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	mouse(A2)
Immunogen	vaccine
Patient MHC/HLA	H2-Kb
Experimental methods
Keywords

Vaccine Details

Vaccine strain	B clade IIIB
Vaccine component	Gag, Pol
Adjuvant	IL-12

Notes

• Transgenic mice expressing a HLA-A2/Kb chimeric protein were vaccinated with either a p17-p24-p51 fusion protein (vG/P-92) or the Gag-Pol precursor protein (vVK1).
• Compared to vVK1, vG/P-92 induced a significant increase in Gag and Pol induced IFNgamma production and CTL responses, and to the epitopes SLYNTVATL and ILKEPVHGV, as determined by Elispot and 51Cr-release assays.

References

Kmieciak2001 Dariusz Kmieciak, Elizabeth Bolesta, Toshio Naito, Jaroslaw Gzyl, Yutaro Kaneko, and Danuta Kozbor. Enhancement of Cellular and Humoral Immune Responses to Human Immunodeficiency Virus Type 1 Gag and Pol by a G/P-92 Fusion Protein Expressing Highly Immunogenic Gag p17/p24 and Pol p51 Antigens. J Hum Virol, 4(6):306-316, Nov-Dec 2001. PubMed ID: 12082397. Show all entries for this paper.

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Displaying record number 52518

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(309-317 NL-43)
Epitope	ILKEPVHGV	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods
Keywords	class I down-regulation by Nef, escape

Notes

• NL43 was passaged in the presence of Nef KEKGGLEGL-specific CTL clones STD11 and KM3, giving rise to rapid selection of escape mutations, including E93G, E93K, K94N+G99R, G95R+G99R, E98K, E98D, G99R, G99E, L100P, and L100I; insertions, deletions, frameshifts and an early stop codon. 34/36 (94%) of sequences carried mutations in the epitope by seven days, 36/36 (100%) by 14 days.
• Several mutations selected by KEKGGLEGL-specific CTL were shown to impair the down regulation of class I MHC by Nef, in particular E93G, E93K, and a truncation mutation at position 51.
• Nef deletion mutants increased 100-fold NL-43 susceptibility to inhibition by CTL specific for epitopes in other proteins, the A2 epitopes ILKEPVHGV in RT and SLYNTVATL in p17 Gag.

References

Ali2003 Ayub Ali, Satish Pillai, Hwee Ng, Rachel Lubong, Douglas D. Richman, Beth D. Jamieson, Yan Ding, M. Juliana McElrath, John C. Guatelli, and Otto O. Yang. Broadly Increased Sensitivity to Cytotoxic T Lymphocytes Resulting from Nef Epitope Escape Mutations. J. Immunol., 171(8):3999-4005, Oct 2003. PubMed ID: 14530319. Show all entries for this paper.

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Displaying record number 52695

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(476-)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	Pol476
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, Flow cytometric T-cell cytokine assay
Keywords	binding affinity, subtype comparisons, computational epitope prediction

Notes

• HLA-A2-restricted HIV-1 CTL epitopes were computationally predicted. Binding affinities for HLA-A*0204, immunogenicity in HLA-A*0201 transgenic mice, and responses to the peptides in 17 HIV-1 infected patients were tested. 31 novel conserved A2 epitopes were detected. An average of 4 epitopes were recognized per patient.
• This epitope was one of the previously identified HLA-A2 epitopes studied.
• 9/17 HIV-infected HLA-A2+ people recognized this epitope.

References

Corbet2003 Sylvie Corbet, Henrik Vedel Nielsen, Lasse Vinner, Sanne Lauemoller, Dominic Therrien, Sheila Tang, Gitte Kronborg, Lars Mathiesen, Paul Chaplin, Søren Brunak, Søren Buus, and Anders Fomsgaard. Optimization and Immune Recognition of Multiple Novel Conserved HLA-A2, Human Immunodeficiency Virus Type 1-Specific CTL Epitopes. J. Gen. Virol., 84(Pt 9):2409-2421, Sep 2003. PubMed ID: 12917462. Show all entries for this paper.

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Displaying record number 52706

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(309-317)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	RT2
Subtype	B
Species (MHC/HLA)	transgenic mouse(A2)
Immunogen	in vitro stimulation or selection, vaccine
Experimental methods
Keywords

Vaccine Details

Vaccine type	peptide
Vaccine component	RT
Adjuvant	Incomplete Freund's Adjuvant (IFA)

Notes

• A virus-like protein scaffold, called E2DISP, derived from pyruvate dehydrogenase multienzyme from Bacillus stearothermophilus has been engineered to display 60 copies of one or more epitopes on a single molecule.
• The E2DISP scaffold displaying pep23 is able to stimulate a Th responses, and peptide RT2, which is a CTL epitope from HIV-1 RT, was able to elicit a CD8+ T cell response in vitro and in a vaccinated HLA-A2 transgenic mouse. Thus the E2DISP scaffold allows cell-entry and access to the class I and class II processing pathways.

References

Domingo2003 Gonzalo J. Domingo, Antonella Caivano, Rossella Sartorius, Pasquale Barba, Malin Bäckström, Dominique Piatier-Tonneau, John Guardiola, Piergiuseppe De Berardinis, and Richard N Perham. Induction of Specific T-Helper and Cytolytic Responses to Epitopes Displayed on a Virus-Like Protein Scaffold Derived from the Pyruvate Dehydrogenase Multienzyme Complex. Vaccine, 21(13-14):1502-1509, 28 Mar 2003. PubMed ID: 12615447. Show all entries for this paper.

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Displaying record number 52776

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay, Tetramer binding
Keywords	responses in children

Notes

• 65 vertically HIV-1 infected children, ages 1-16, the majority undergoing ART, were analyzed in regard to their plasma viremia and CD4+ and CD8+ T cell counts, and CD8+ T cell responses.
• Using vaccina expressed Gag, Pol, Env, Rev, Nef in target cells in an Elispot assay, 85% of the children recognized at least one HIV antigen. The strong CD8+ T cell responses were directed against Pol, followed by Gag and Nef. Children younger than 4 had significantly weaker responses (7/14 had no response) than older children (only 1/32 had no response, and responses were greater in magnitude).
• SLYNTVATL and ILKEPVHGV tetramers were used to quantitate specific responses. 49 children in an expanded cohort carried HLA-A2. 1/11 children under 3 years of age had detectable CD8+ T-cell responses to SLYNTVATL, 2/11 to ILKEPVHGV. Among children over 3, 11/38 recognized SLYNTVATL and 9/38 recognized ILKEPVHGV.
• Older children that maintained a CD4 count greater than 400 cells/ul tended to have stronger CTL responses.

References

Sandberg2003 Johan K. Sandberg, Noam M. Fast, Kimberly A. Jordan, Scott N. Furlan, Jason D. Barbour, Glenn Fennelly, Joanna Dobroszycki, Hans M. L. Spiegel, Andrew Wiznia, Michael G. Rosenberg, and Douglas F. Nixon. HIV-Specific CD8+ T Cell Function in Children witH Vertically Acquired HIV-1 Infection is Critically Influenced by Age and the State of the CD4+ T Cell Compartment. J. Immunol., 170(8):4403-4410, Apr 2003. PubMed ID: 12682278. Show all entries for this paper.

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Displaying record number 52781

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(309-317)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	(A2)
Immunogen	HIV-1 infection
Patient MHC/HLA	A2, A3, B27, B51; A2, A3, B27, B57; A2, A23, B57
Experimental methods	CD8 T-cell Elispot - IFNγ, Cytokine production, Intracellular cytokine staining, Tetramer binding
Keywords	assay or method development, memory cells

Notes

• This study compares assay methods for testing CTL responses using samples from 20 HIV+ patients. The study compares ELISpot, tetramer-binding, and intracellular IFN-γ. Tetramer-binding analysis was performed with Gag (SLYNTVATL) or Pol (ILKEPVHGV) tetramers. Antigen presentation using recombinant vaccinia viruses (rVVs) encoding HIV-LAI Gag, Pol, Env, Nef, Tat and Vif proteins was compared to peptide panels. HIV antigen recognition in memory CTLs was measured by chromium release assay and compared to effector/memory CD8+ T cells in an IFN-γ ELISpot assay.
• Results: IFN-γ Elispot and flow cytometry gave similar frequencies of HIV specific CD8+ Tcells. Tetramer-binding analysis was most sensitive. Pools of peptides and the sum of frequencies of individual peptides were comparable. Elispot assays using peptides were more sensitive than assays using vaccinia expressed proteins. Cr release and Elispot against rVVs gave comparable memory cell responses 2/3s of the time.
• 3/7 HLA-A2+ patients recognized this epitope.

References

Sun2003 Y. Sun, E. Iglesias, A. Samri, G. Kamkamidze, T. Decoville, G. Carcelain, and B. Autran. A Systematic Comparison of Methods to Measure HIV-1 Specific CD8 T Cells. J. Immunol. Methods, 272(1-2):23-34, 15 Jan 2003. PubMed ID: 12505709. Show all entries for this paper.

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Displaying record number 52787

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(309-317 NL43)
Epitope	ILKEPVHGV	Epitope Alignment
		Show epitope variants
Epitope Name	IV9
Subtype	B
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods	CTL suppression of replication, Chromium-release assay
Keywords	escape

Notes

• Virus was cultured in the presence of CTL lines specific for 4 different epitopes (SLYNTVATL, ILKEPVHGV, IEIKDTKEAL, and KEKGGLEGL) to study the emergence of escape mutations. Escape varied between clones for the same epitope, and between different epitopes. Gag and RT epitope escape, if it occurred at all, tended to be monoclonal and within the epitope, indicating strong fitness constraints, while the Nef epitope escape was rapid, polyconal, and sometimes the result of upstream frameshifts.
• There was one cloned cell line that recognized ILKEPVHGV, 68A62. After 2 weeks of passaging HIV-1 in the presence of 68A62, the mutated epitope ilkeLvhgv was found in 6/12 sequences.

References

Yang2003 Otto O Yang, Phuong Thi Nguyen Sarkis, Ayub Ali, Jason D Harlow, Christian Brander, Spyros A Kalams, and Bruce D Walker. Determinant of HIV-1 Mutational Escape from Cytotoxic T Lymphocytes. J. Exp. Med., 197(10):1365-1375, May 2003. PubMed ID: 12743169. Show all entries for this paper.

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Displaying record number 53035

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Country	Netherlands
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	HIV exposed persistently seronegative (HEPS)

Notes

• A high-risk seronegative group of 29 homosexual men showed reduced cellular in vitro susceptibility for HIV infection and enhanced production of RANTES compared to 15 men who went on to seroconvert. Significantly higher frequencies of HLA A*11, A*31 and Cw*15 were also found in the high risk seronegative men. Both groups of men had low frequencies of HIV-1 specific CD8+ T-cells, which may signify exposure more than protection from infection.
• 2/11 HLA A2+ infection-resistant men, compared to 1/9 pre-seroconversion men who went on to become infected, reacted to this epitope.

References

Koning2004 Fransje A. Koning, Christine A. Jansen, Jos Dekker, Richard A. Kaslow, Nicole Dukers, Debbie van Baarle, Maria Prins, and Hanneke Schuitemaker. Correlates of Resistance to HIV-1 Infection in Homosexual Men with High-Risk Sexual Behaviour. AIDS, 18(8):1117-1126, 21 May 2004. PubMed ID: 15166527. Show all entries for this paper.

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Displaying record number 53152

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(309-317)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	RT-IV9
Subtype	B
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods	Chromium-release assay
Keywords	binding affinity, TCR usage, characterizing CD8+ T cells

Notes

• Killing efficiency of CTLs and their ability to suppress viral replication is shown to depend more on epitope specificity than to antigenic avidity. Different clones recognizing the same epitope had similar killing efficiency despite their variation in avidity. Nef specific CTL clones tended to be most inhibitory, followed by Gag, then by RT specific clones, regardless of avidity.
• 2/14 CTL T-cell clones tested were specific for RT/IV9. Under conditions of excess peptide (100ug/ml), there was no difference in their lytic potential; all possessed similar effector capacity. Avidity was measured as the sensitizing dose of peptide required for 50% of maximal killing (SD50), which varied from 20 pg/ml to 100 ng/ml, over four orders of magnitude for all 14 epitopes. The SD50 values for the two RT/IV9 clones were very different, 50 and 20,000 pg/ml.

References

Yang2003a Otto O. Yang, Phuong T. Nguyen Sarkis, Alicja Trocha, Spyros A. Kalams, R. Paul Johnson, and Bruce D. Walker. Impacts of Avidity and Specificity on the Antiviral Efficiency of HIV-1-Specific CTL. J. Immunol., 171(7):3718-3724, 1 Oct 2003. PubMed ID: 14500671. Show all entries for this paper.

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Displaying record number 53355

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	( B consensus)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Subtype	B
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Patient MHC/HLA	A2, A3, B62, B8, Cw10, Cw7
Country	United States
Experimental methods	Chromium-release assay, Cytokine production, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords	assay or method development, memory cells, characterizing CD8+ T cells

Notes

• Using a flow-cytometric cytotoxicity assay based on caspase-3 activation in dying target cells, it was shown that the subset of HIV-1-specific CD8+ T cells secreting both IFN-gamma and TNF-alpha exhibit stronger cytotoxic activity than those secreting only IFN-gamma. These cells also exhibited stronger intracellular perforin expression. No association between HIV-1-specific CD8+ T-cell maturation phenotypes and intracellular perforin expression was found.
• 1/9 individuals recognized this epitope.

References

Lichterfeld2004b Mathias Lichterfeld, Xu G. Yu, Michael T. Waring, Stanley K. Mui, Mary N. Johnston, Daniel Cohen, Marylyn M. Addo, John Zaunders, Galit Alter, Eunice Pae, Daryld Strick, Todd M. Allen, Eric S. Rosenberg, Bruce D. Walker, and Marcus Altfeld. HIV-1-Specific Cytotoxicity Is Preferentially Mediated by a Subset of CD8+ T Cells Producing both Interferon-gamma and Tumor Necrosis Factor-alpha. Blood, 104(2):487-394, 15 Jul 2004. PubMed ID: 15059848. Show all entries for this paper.

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Displaying record number 53388

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(309-317)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods	Chromium-release assay
Keywords	assay or method development

Notes

• Using IL7 or IL15 in culturing of HIV-1-specific CTL clones was inferior to using IL-2 alone; the addition of these cytokines to IL-2 did not show any advantage. Neither proliferation, survival, nor lytic capacity of HIV-1-specific CTLs was significantly enhanced by addition of IL7 or IL15.

References

Lubong2004 Rachel Lubong, Hwee L. Ng, Christel H. Uittenbogaart, and Otto O. Yang. Culturing of HIV-1-Specific Cytotoxic T Lymphocytes with Interleukin-7 and Interleukin-15. Virology, 325(2):175-180, 1 Aug 2004. PubMed ID: 15246257. Show all entries for this paper.

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Displaying record number 53398

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 exposed seronegative
Patient MHC/HLA	A*02, A*30, B*15, B*44:02
Experimental methods	T-cell Elispot, Tetramer binding
Keywords	HIV exposed persistently seronegative (HEPS)

Notes

• HIV-specific T-cell response was tested in patients exposed to blood from a patient with highly replicating HIV; these patients were nosocomially infected with HBV, but uninfected with HIV. HIV-specific T-cell responses were directed to structural and non-structural HIV proteins in 2 patients, suggesting that the virus replicated in these patients sufficiently to prime a cell-mediated immune response that protected them from HIV infection.
• This patient responded to 4/8 HIV epitopes tested in an IFNgamma EliSpot assay or tetramer assay. Responses were detected 8 and 28 weeks after exposure. A response to ILKEPVHGV was detected by both assays.

References

Missale2004 Gabriele Missale, Laura Papagno, Amalia Penna, Massimo Pilli, Alessandro Zerbini, Piero Vitali, Giovanni Pieroni, Simona Urbani, Jacopo Uggeri, Susana Pinheiro, Sarah Rowland-Jones, and Carlo Ferrari. Parenteral Exposure to High HIV Viremia Leads to Virus-Specific T Cell Priming without Evidence of Infection. Eur. J. Immunol., 34(11):3208-3215, Nov 2004. PubMed ID: 15459901. Show all entries for this paper.

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Displaying record number 53402

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol
Epitope	ILKEPVHGV	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Country	United Kingdom
Experimental methods	Intracellular cytokine staining, T-cell Elispot, Tetramer binding
Keywords	rate of progression, acute/early infection, characterizing CD8+ T cells

Notes

• Acute HIV-1 infection induces massive activation of HIV-specific and non-HIV-specific CD8+ T-cells resulting in differentiation of these cells. High differentiation of CD8+ T-cells is correlated with disease progression. Differentiation is a natural process but it can be driven by elevated immune activation, such as in HIV infection.

References

Papagno2004 Laura Papagno, Celsa A. Spina, Arnaud Marchant, Mariolina Salio, Nathalie Rufer, Susan Little, Tao Dong, Gillian Chesney, Anele Waters, Philippa Easterbrook, P. Rod Dunbar, Dawn Shepherd, Vincenzo Cerundolo, Vincent Emery, Paul Griffiths, Christopher Conlon, Andrew J. McMichael, Douglas D. Richman, Sarah L. Rowland-Jones, and Victor Appay. Immune Activation and CD8+ T-Cell Differentiation towards Senescence in HIV-1 Infection. PLoS Biol., 2(2):E20, Feb 2004. PubMed ID: 14966528. Show all entries for this paper.

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Displaying record number 53460

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	(309-317)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	RT2
Species (MHC/HLA)	transgenic mouse(A2)
Immunogen	vaccine
Experimental methods	Chromium-release assay
Keywords	vaccine antigen design

Vaccine Details

Vaccine type	bacteriophage coat protein, dihydrolipoyl acetyltransferase E2 protein, of Bacillus stearothermophilus
Vaccine component	RT

Notes

• An RT T-helper (KDSWTVNDIQKLVGK) that can be promiscuously presented by multiple HLA-DR molecules, and an RT CTL epitope (ILKEPVHGV) presented by HLA-A2, were displayed using two different antigen presentation systems, bacteriophage virions or E2 protein scaffolds. Both systems enabled display of the epitopes in a mouse model system to the immune system. CTL responses were detected in immunized mice, and were processed correctly for both class I and class II presentation.

References

DeBerardinis2003 Piergiuseppe De Berardinis, Rossella Sartorius, Antonella Caivano, Dina Mascolo, Gonzalo J. Domingo, Giovanna Del Pozzo, Muriel Gaubin, Richard N. Perham, Dominique Piatier-Tonneau, and John Guardiola. Use of Fusion Proteins and Procaryotic Display Systems for Delivery of HIV-1 Antigens: Development of Novel Vaccines for HIV-1 Infection. Curr. HIV Res., 1(4):441-446, Oct 2003. PubMed ID: 15049429. Show all entries for this paper.

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Displaying record number 53500

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Subtype	B
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	subtype comparisons, escape, characterizing CD8+ T cells, viral fitness and reversion

Notes

• Two-thirds of all mutations arising in non-envelope proteins during the transition from acute to chronic infection were found to be due to either CD8 T-cell-associated selective pressures or reversion of HLA-I-associated mutations selected in a previous host.The predominance of escape mutations at highly polymorphic sites was observed across different HIV-1 clades.
• Two escape mutations, at positions 3 ilRepvhgv, and 9 ilkepvhgA, were found not to correspond to the most polymorphic residues in the epitope.

References

Allen2005a Todd M. Allen, Marcus Altfeld, Shaun C. Geer, Elizabeth T. Kalife, Corey Moore, Kristin M. O'Sullivan, Ivna DeSouza, Margaret E. Feeney, Robert L. Eldridge, Erica L. Maier, Daniel E. Kaufmann, Matthew P. Lahaie, Laura Reyor, Giancarlo Tanzi, Mary N. Johnston, Christian Brander, Rika Draenert, Jurgen K. Rockstroh, Heiko Jessen, Eric S. Rosenberg, Simon A. Mallal, and Bruce D. Walker. Selective Escape from CD8+ T-Cell Responses Represents a Major Driving Force of Human Immunodeficiency Virus Type 1 (HIV-1) Sequence Diversity and Reveals Constraints on HIV-1 Evolution. J. Virol., 79(21):13239-13249, Nov 2005. PubMed ID: 16227247. Show all entries for this paper.

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Displaying record number 53588

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(309-317)
Epitope	ILKEPVHGV	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, HLA binding
Keywords	acute/early infection, optimal epitope

Notes

• The most frequently targeted HLA-A*02-restricted CD8+ T-cell epitopes in chronic infection were significantly less frequently recognized during primary infection.
• ILKEPVHGV was targeted in 54% of 74 A*02+ chronically infected individuals, but only 1/14 acutely infected A2+ individuals.

References

Altfeld2005a Marcus Altfeld, Todd M. Allen, Elizabeth T. Kalife, Nicole Frahm, Marylyn M. Addo, Bianca R. Mothe, Almas Rathod, Laura L. Reyor, Jason Harlow, Xu G. Yu, Beth Perkins, Loren K. Robinson, John Sidney, Galit Alter, Mathias Lichterfeld, Alessandro Sette, Eric S. Rosenberg, Philip J. R. Goulder, Christian Brander, and Bruce D. Walker. The Majority of Currently Circulating Human Immunodeficiency Virus Type 1 Clade B Viruses Fail To Prime Cytotoxic T-Lymphocyte Responses against an Otherwise Immunodominant HLA-A2-Restricted Epitope: Implications for Vaccine Design. J. Virol., 79(8):5000-5005, Apr 2005. PubMed ID: 15795285. Show all entries for this paper.

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Displaying record number 53708

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Country	Germany
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, escape, variant cross-reactivity, optimal epitope

Notes

• An HLA-B13-restricted optimal epitope was defined in Nef, RI9. The frequency of CTLs specific for this epitope in B13-positive patients exceeded the number of CTLs against other epitopes, indicating that this is a dominant epitope in B13-positive subjects. Three B13-positive patients who had an immunodominant response to this epitope were good controllers of their infection, with low viral loads over long periods.
• 5 HLA A2+ B13+ patients were found to make an immunodominant response to the B13 epitope RI9. 0/5 recognized the A2 epitope ILKEPVHGV, and only 1/5 recognized the A2 epitope SLYNTAVTL, with a much lower frequency than the B13 response.

References

Harrer2005b Ellen G. Harrer, Silke Bergmann, Kathrin Eismann, Marion Rittmaier, Andreas Goldwich, Sandra M. Müller, Bernd M. Spriewald, and Thomas Harrer. A Conserved HLA B13-Restricted Cytotoxic T Lymphocyte Epitope in Nef is a Dominant Epitope in HLA B13-Positive HIV-1-Infected Patients. AIDS, 19(7):734-735, 29 Apr 2005. PubMed ID: 15821402. Show all entries for this paper.

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Displaying record number 53719

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(476-484 BRU)
Epitope	ILKEPVHGV	Epitope Alignment
Subtype	B, CRF02_AG
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Country	Cote D'Ivoire
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	subtype comparisons

Notes

• CD8+ T-cells from HIV-1 CRF02_AG-infected Ivorians could recognize clade B epitopes. No difference was observed in the number of recognized peptide pools between nine French subtype B infected study subjects, and nine CRF02_AG infected Ivorian subjects.
• This epitope was recognized by 2/9 CRF02_AG-infected Ivorians, and 1/9 B-infected French subjects.

References

Inwoley2005 André Inwoley, Patricia Recordon-Pinson, Marion Dupuis, Jessintha Gaston, Mathieu Genête, Albert Minga, Franck Letourneur, François Rouet, Jeannine Choppin, Hervé Fleury, Jean-Gérard Guillet, Muriel Andrieu, and ANRS 1220 PRIMO-CI Study Group. Cross-Clade Conservation of HIV Type 1 Nef Immunodominant Regions Recognized by CD8+ T Cells of HIV Type 1 CRF02\_AG-Infected Ivorian (West Africa). AIDS Res. Hum. Retroviruses, 21(7):620-628, Jul 2005. PubMed ID: 16060833. Show all entries for this paper.

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Displaying record number 53803

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(77-85)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IL9
Subtype	B
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 exposed seronegative, HIV-1 infection
Country	Canada
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	HIV exposed persistently seronegative (HEPS), immunodominance, genital and mucosal immunity, characterizing CD8+ T cells

Notes

• CD8 T-cell responses were studied in individuals who remained seronegative in spite of being mucosally (group 1) or intravenously (group 2) exposed to HIV-1. A similar proportion of subjects from each group recognized at least 1 HIV peptide, and they recognized peptides with similar cumulative intensity. The proportion of responding individuals in both groups was significantly greater than in a low-risk, negative control group. One exposed uninfected subject recognized 7 epitopes.
• HLA-A*0201 epitopes that are immunodominant in chronically infected individuals were rarely stimulatory in exposed uninfected individuals. SLYNTVATL was recognized by one HLA A2+ individual in each group (1/11 vs 1/5), while none of the exposed uninfected individuals tested responded to ILKEPVHGV. In contrast, chronically infected subjects recognized these epitopes at a frequency of 69% and 31%, respectively.

References

Makedonas2005a George Makedonas, Julie Bruneau, Michel Alary, Christos M. Tsoukas, Catherine M. Lowndes, François Lamothe, and Nicole F. Bernard. Comparison of HIV-Specific CD8 T-Cell Responses among Uninfected Individuals Exposed to HIV Parenterally and Mucosally. AIDS, 19(3):251-259, 18 Feb 2005. PubMed ID: 15718835. Show all entries for this paper.

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Displaying record number 53859

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Country	Germany
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay
Keywords	HAART, ART, TCR usage, characterizing CD8+ T cells, optimal epitope

Notes

• CTL responses to 3 HLA-A2-restricted epitopes were investigated in 51 HIV-1 infected HLA-A2+ individuals. The most prevalent response was seen for IV9, followed by SL9. The VL9 epitope was not recognized. There was a significant correlation of CTL activity to the CD8 counts in peripheral blood, but no correlation to CD4 counts, viral load, or antiviral therapy.
• 37.3% of the individuals recognized ILKEPVHGV.
• All analyzed mutations for RT-IV9 epitope could decrease or abrogate CTL recognition dependent on the CTL clones tested, but all were fully immunogenic for other CTL clones. The ilkDpvhgv, ilkepvhEv, Rlkepvhgv and ilRepvhgv variants were tested.

References

Schmitt-Haendle2005 Matthias Schmitt-Haendle, Oliver Bachmann, Ellen Harrer, Barbara Schmidt, Michael Bäuerle, and Thomas Harrer. Recognition Patterns of HLA-A2-Restricted Human Immunodeficiency Virus-1-Specific Cytotoxic T-Lymphocytes in a Cohort of HIV-1-Infected Individuals. Viral Immunol., 18(4):627-636, 2005. PubMed ID: 16359229. Show all entries for this paper.

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Displaying record number 54231

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	A2-IV9(RT)
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, immunodominance, early-expressed proteins

Notes

• Immunodominant HIV epitopes in early, primary infection of CTLs were identified and the relative contributions of immune responses restricted to individual HLA class I molecules were studied.
• This epitope-HLA combination was recognized. The most frequently recognized epitopes also elicited the greatest CTL response.
• HIV-1 Epitope sequence variability was not correlated with immunodominant versus immune sub-dominant responses.
• HLA-B*57 and HLA-B*27 restricted responses were the strongest in these early and acute infections - due to dominant responses to a single epitope in each case (TW10 for B*57 and KK10 for B*27).
• In the presence of HLA-B*57 and HLA-B*27 restricted responses, the relative contributions of other restricting HLA dropped greatly.

References

Altfeld2006 Marcus Altfeld, Elizabeth T. Kalife, Ying Qi, Hendrik Streeck, Mathias Lichterfeld, Mary N. Johnston, Nicole Burgett, Martha E. Swartz, Amy Yang, Galit Alter, Xu G. Yu, Angela Meier, Juergen K. Rockstroh, Todd M. Allen, Heiko Jessen, Eric S. Rosenberg, Mary Carrington, and Bruce D. Walker. HLA Alleles Associated with Delayed Progression to AIDS Contribute Strongly to the Initial CD8+ T Cell Response against HIV-1. PLoS Med., 3(10):e403, Oct 2006. PubMed ID: 17076553. Show all entries for this paper.

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Displaying record number 54759

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(309-317)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods	Chromium-release assay, Other
Keywords	binding affinity

Notes

• Standard assays like ELISpot, ICS and tetramer staining do not measure antiviral activity of HIV-infected CTLs, but use exogenous synthetic peptides on uninfected cells, or HLA tetramers. Similarly, functional avidity assesses CTL activity against uninfected target cells. Here functional avidity is compared to the efficiency of actual infected cells' recognition and killing, revealing a sharp threshold between CTL immune antiviral activity and lack of infected cell recognition.
• As previously shown, epitopes and their variants spanned orders of magnitude of SD50. Likewise, CTL clearance of infected cells varied from 0 to 100% with epitope sequence variation. Moreover, direct suppression of HIV-1 replication by CTLs also varied with epitope variant.
• When killing efficiency (KE) using virus-infected cells was compared to functional avidity using synthetic peptides, there was a narrow threshold separating maximal killing from almost none. Since different SL9-specific clones had similar KEs, which were vastly different from RL10-specific CTL KEs, it was obvious that KEs varied with epitope sequence too. Finally, a strong correlation between KE and inhibition of viral replication was also seen.
• This epitope, ILKEPVHGV, showed marked differences in its functional avidity as well as killing efficiency, when compared to its variants ILKdPVHGV, ILKnPVHGV, ILKdPVHGa, ILKtPVHGV, ILrEPVHGV, ILKEsVHGV, ILKEtVHGV, ILKEPVHGa, ILKEPVHeV, ILKqPVHGV, IiKEPVHGV, ILrtPVHGV, ILKEPVHrV, ILKEPlHGV, kLKEPVHGV and ILKElVHGV.

References

Bennett2007 Michael S. Bennett, Hwee L. Ng, Mirabelle Dagarag, Ayub Ali, and Otto O. Yang. Epitope-Dependent Avidity Thresholds for Cytotoxic T-Lymphocyte Clearance of Virus-Infected Cells. J. Virol., 81(10):4973-4980, May 2007. PubMed ID: 17329324. Show all entries for this paper.

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Displaying record number 54880

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection, vaccine
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	vaccine-induced immune responses, characterizing CD8+ T cells

Vaccine Details

Vaccine type	canarypox, canarypox prime with recombinant protein boost
Vaccine strain	B clade BRU, B clade LAI, B clade MN, multiple epitope immunogen
Vaccine component	Gag, gp120, gp41, Nef, Pol, Protease

Notes

• CD8+ T-cell function induced by HIV-1 immunogens and natural infection was compared. Natural infections consisted of early, chronic, and long term nonprogressors.
• B27- and B57-restricted CD8+ T cells from nonprogressors exhibited greater expansion than those restricted by other alleles, providing an explanation for the observed association between HLA-B27/B57 and control of HIV-1 infection.

References

Horton2006 Helen Horton, Ian Frank, Ruth Baydo, Emilie Jalbert, Justin Penn, Sean Wilson, John P. McNevin, Matthew D. McSweyn, Deborah Lee, Yunda Huang, Stephen C. De Rosa, and M. Juliana McElrath. Preservation of T Cell Proliferation Restricted by Protective HLA Alleles Is Critical for Immune Control of HIV-1 Infection. J. Immunol., 177(10):7406-7415, 15 Nov 2006. PubMed ID: 17082660. Show all entries for this paper.

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Displaying record number 55183

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Country	Kenya
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Tetramer binding
Keywords	responses in children, rate of progression

Notes

• A study of long-term surviving children in Kenya revealed CD8 T-cell responses in all progression groups. The most striking atttribute of long term surviving children was strong CD4 T-cell responses, which may be significant in delaying disease progression.
• Response detected in 1 LTNP child and 1 early non-progressive child.

References

Chakraborty2005 Rana Chakraborty, Anne-Sophie Morel, Julian K. Sutton, Victor Appay, Ruth M. Ripley, Tao Dong, Tim Rostron, Simon Ogola, Tresa Palakudy, Rachel Musoke, Angelo D'Agostino, Mary Ritter, and Sarah L. Rowland-Jones. Correlates of Delayed Disease Progression in HIV-1-Infected Kenyan Children. J. Immunol., 174(12):8191-8199, 15 Jun 2005. PubMed ID: 15944328. Show all entries for this paper.

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Displaying record number 55397

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location
Epitope	ILKEPVHGV	Epitope Alignment
		Show epitope variants
Epitope Name	Pol 476
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Country	Denmark
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords	immunodominance

Notes

• 11 HLA-A2+ (A*0201, A*0220, A*0234 or A*0236), patients' HIV were sequenced. Of 28 epitopes studied, most were conserved and elicited a subdominant CTL response. 9 epitopes in 7 proteins showed T-cell cross reaction. These epitopes were optimized to induce more immunogenic but cross-reacting responses.
• Epitopes in Gag, Pol, Env, Nef were more conserved than epitopes in shorter proteins Vpu, Vif, Vpr and Rev. Most natural epitopes were untargeted or targeted by 1 or 2 patients.
• Immunodominant control epitope Pol 476, ILKEPVHGV, was found in 9 patients but only 4 had CTL immune responses to it.

References

Thorn2007 Mette Thorn, Sheila Tang, Dominic Therrien, Henrik Kløverpris, Lasse Vinner, Gitte Kronborg, Jan Gerstoft, Sylvie Corbet, and Anders Fomsgaard. Sequence Conservation of Subdominant HLA-A2-Binding CTL Epitopes in HIV-1 Clinical Isolates and CD8+ T-Lymphocyte Cross-Recognition May Explain the Immune Reaction in Infected Individuals. APMIS, 115(6):757-768, Jun 2007. PubMed ID: 17550385. Show all entries for this paper.

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Displaying record number 55742

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	Pol498
Subtype	B
Species (MHC/HLA)	human(A2)
Immunogen	vaccine
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	vaccine antigen design

Vaccine Details

Vaccine type	DNA, polyepitope
Vaccine component	other

Notes

• DNA vaccine EP HIV-1090 evaluation in patients receiving ART was done. This vaccine is composed of multiple CTL epitopes, all associated with certain HLA supertypes. Differences of CTL response rate in vaccine and placebo recipients however, was not significant.
• ILKEPVHGV is a Pol epitope encoded in the EP HIV-1090 polyepitope vaccine.

References

Wilson2008 Cara C. Wilson, Mark J. Newman, Brian D. Livingston, Samantha MaWhinney, Jeri E. Forster, Jim Scott, Robert T. Schooley, and Constance A. Benson. Clinical Phase 1 Testing of the Safety and Immunogenicity of an Epitope-Based DNA Vaccine in Human Immunodeficiency Virus Type 1-Infected Subjects Receiving Highly Active Antiretroviral Therapy. Clin. Vaccine Immunol., 15(6):986-994, Jun 2008. PubMed ID: 18400976. Show all entries for this paper.

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Displaying record number 55751

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol
Epitope	ILKEPVHGV	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A2)
Immunogen	peptide-HLA interaction
Experimental methods	Chromium-release assay, Other
Keywords	TCR usage

Notes

• Unlike LTNPs, most patients cannot produce enough conserved-epitope-recognizing, HIV-specific CTLs to curtail infection. Here, primary CTLs are reprogrammed by RNA electroporation of epitope-specific TCRs to produce proinflammatory cytokines and to lyse target cells presenting the appropriate epitope. For the first time functional transfer of epitope-specific TCRs is shown to be feasible.
• T2 cells loaded with epitope ILKEPVHGV, were lysed upon contact with the their corresponding TCRs inserted into CTL clones by RNA electroporation.

References

Hofmann2008 Christian Hofmann, Thomas Harrer, Verena Kubesch, Katja Maurer, Karin J. Metzner, Kathrin Eismann, Silke Bergmann, Matthias Schmitt-Haendle, Gerold Schuler, Jan Dörrie, and Niels Schaft. Generation of HIV-1-Specific T Cells by Electroporation of T-Cell Receptor RNA. AIDS, 22(13):1577-1582, 20 Aug 2008. PubMed ID: 18670216. Show all entries for this paper.

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Displaying record number 55846

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(464-472)
Epitope	ILKEPVHGV	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Country	Switzerland
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Other
Keywords	HAART, ART

Notes

• By following T-cell function in ART-regimented patients over time, it was shown that ART resulted in reduced viral replication and the restoration of CTLs to polyfunctionality. It is concluded that in vivo antigenic exposure during declining viremia has a positive influence on CTL function.
• Epitope ILKEPVHGV was used to interrogate CTL function in 37 chronically infected HIV-1 positive subjects, with respect to cytokine production.

References

Rehr2008 Manuela Rehr, Julia Cahenzli, Anna Haas, David A. Price, Emma Gostick, Milo Huber, Urs Karrer, and Annette Oxenius. Emergence of Polyfunctional CD8+ T Cells after Prolonged Suppression of Human Immunodeficiency Virus Replication by Antiretroviral Therapy. J. Virol., 82(7):3391-404, Apr 2008. PubMed ID: 18199637. Show all entries for this paper.

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Displaying record number 55907

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9(RT)
Subtype	B
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Country	China
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	chronic infection

Notes

• 49 ART-naive chronically HIV-1 infected Chinese subjects' CTLs were tested with 413 OLPs in IFN-γ assays, determining optimal epitopes specific for Chinese Clade B HIV-1 sequences.
• An inverse correlation was found between CTL response and viral load.
• Targeted peptides have lower entropy than peptides that are not CTL targeted. This correlation is independent of HLA-restriction.
• Previously described HLA-A2-restricted epitope ILKEPVHGV elicited an immune response in Chinese HIV-1 positive subjects as part of peptide ELAENREILKEPVHGVYY.
• 5 of the 55 HLA-A2 carriers responded to ILKEPVHGV-containing peptide with average magnitude of CTL response of 189 SFC/million PBMC (author communication and Fig.1).

References

Zhai2008 Song Zhai, Yan Zhuang, Yang Song, Shu Li, Dedong Huang, Wenzhen Kang, Xinhong Li, Qi Liao, Yanhou Liu, Zhongfang Zhao, Yichen Lu, and Yongtao Sun. HIV-1-Specific Cytotoxic T Lymphocyte (CTL) Responses Against Immunodominant Optimal Epitopes Slow the Progression of AIDS in China. Curr. HIV Res., 6(4):335-350, Jun 2008. PubMed ID: 18691032. Show all entries for this paper.

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Displaying record number 56063

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(476-)
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	Pol476
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Country	Denmark
Experimental methods	Flow cytometric T-cell cytokine assay
Keywords	rate of progression, acute/early infection

Notes

• Comparative genetic and immunological study was conducted of two subjects - patient DK1 with no viremia for >10 years after transient ART and despite continued sexual contact with patient UG1 (his wife) who was an HIV-1-positive non-controller.
• DK1 and UG1 shared most crossover points of recombination but while DK1 had subtype A1 Env, UG1's Env was subtype D. In the shared subtype A1/D regions, homology between the patients' sequences was 98%.
• Out of 23 conserved HLA-A02 epitopes, HLA-A2+ DK1 produced CTL response and IFN-gamma response only to epitope ILKEPVHGV.
• DK1 produced neutralizing antibody only to homologous isolates. It is suggested that early, transient ART may have resulted in full control of viremia and disease via the very narrow specific CTL response and neutralizing antibody.
• DK1 responded to HLA-A02-restricted Pol control epitope ILKEPVHGV. ILKEPVHGV also elicited response in a cohort of 11 other HIV-1+ HLA-A2+ patients.

References

Fomsgaard2008 Anders Fomsgaard, Lasse Vinner, Dominic Therrien, Louise B. Jørgensen, Claus Nielsen, Lars Mathiesen, Court Pedersen, and Sylvie Corbet. Full-Length Characterization of A1/D Intersubtype Recombinant Genomes from a Therapy-Induced HIV Type 1 Controller during Acute Infection and His Noncontrolling Partner. AIDS Res. Hum. Retroviruses, 24(3):463-472, Mar 2008. PubMed ID: 18373434. Show all entries for this paper.

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Displaying record number 56140

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(309-317)
Epitope	ILKEPVHGV	Epitope Alignment
		Show epitope variants
Epitope Name	IV9
Subtype	B
Species (MHC/HLA)	human, transgenic mouse(A2)
Immunogen	in vitro stimulation or selection, vaccine
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay
Keywords	variant cross-reactivity

Vaccine Details

Vaccine type	peptide
Adjuvant	Incomplete Freund's Adjuvant (IFA)

Notes

• To identify immunogenically optimized peptide epitopes for use in vaccines, two strategies were used. The first studied rare mutant epitopes that were effective in generating a cross-reactive immune response against a range of mutants. The second method was to use a synthetic combinatorial library of peptides and screen for highly effective responses against one epitope (TV9, TLNAWVKVV) and its mutants. Candidate epitopes were tested in HLA-A2 transgenic mice as well as ex vivo human lymphocytes.
• Mutants of epitope IV9 when tested in transgenic mice, showed that the consensus was strongly immunogenic, but the most common mutant, ILKdPVHGV was not especially immunogenic or cross-reactive. Rare mutant, ILKEPVHrV, was highly immunogenic, and cross-reactive to the consensus. Sequences ILrEPiHGV and ILKEPVHGi were also cross-reactive to the consensus. Other mutants were ILKEPVHGa, ILrtPVHGV, IiKEPVHGV, ILrkPVHeV and ILKdPVHkV.

References

Blondelle2008 Sylvie E. Blondelle, Rosa Moya-Castro, Keiko Osawa, Kim Schroder, and Darcy B. Wilson. Immunogenically Optimized Peptides Derived from Natural Mutants of HIV CTL Epitopes and Peptide Combinatorial Libraries. Biopolymers, 90(5):683-694, 2008. PubMed ID: 18481808. Show all entries for this paper.

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Displaying record number 56728

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Species (MHC/HLA)	transgenic mouse(A2)
Immunogen	vaccine
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	variant cross-reactivity, vaccine antigen design

Vaccine Details

Vaccine type	peptide, polyepitope

Notes

• The immunogenicity of 3 well-documented A2 epitopes, Gag-TV9, Gag-SL9, and RT-IV9 and their mutants were studied in mice. The conservative mutants (both common and rare) were similar to or less immunogenic than the wild type, while the rare non-conservative mutants were highly immunogenic. Cross-recognition of mutants was highest among mutants occurring at potential TCR contact positions. The authors advocate multi-variant epitope-based vaccine strategies.
• One common variant and two rare variants to IV9 were tested. The rare variant ILKEPVHrV was highly immunogenic. The common variant ILKdPVHGV had diminished response comapred to the original epitope. The rare variant IiKEPVHGV was not immunogenic.
• ILKEPVHrV cross reacted with the original epitope IV9.

References

Blondelle2009 Sylvie E. Blondelle, Rosa Moya, Kim Schroder, Keiko Osawa, and Darcy B. Wilson. Natural Mutants of HIV CTL Epitopes with Enhanced Immunogenicity as Potential Vaccine Candidates. Adv. Exp. Med. Biol., 611:379-382, 2009. PubMed ID: 19400233. Show all entries for this paper.

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Displaying record number 57215

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Country	Kenya
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	mother-to-infant transmission

Notes

• HIV-1 peptide-specific IFN-γ responses were measured over the first year of life for vertically-infected infants. Late-infected infants (between months 1 and 12) had responses that were more rapid and more focused than those infected before 1 month of life.
• 1/4 infants tested recognized ILKE/DPVHGV.
• Variants of this peptide were ILKE/DPVHGV (ILKePVHGV and ILKdPVHGV).

References

Lohman-Payne2009 B. Lohman-Payne, J. A. Slyker, B. A. Richardson, C. Farquhar, M. Majiwa, E. Maleche-Obimbo, D. Mbori-Ngacha, J. Overbaugh, S. Rowland-Jones, and G. John-Stewart. Infants with Late Breast Milk Acquisition of HIV-1 Generate Interferon-gamma Responses More Rapidly than Infants with Early Peripartum Acquisition. Clin. Exp. Immunol., 156(3):511-517, Jun 2009. PubMed ID: 19438605. Show all entries for this paper.

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Displaying record number 57627

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	ILK
Subtype	A, B, C
Species (MHC/HLA)	transgenic mouse(A2)
Immunogen	vaccine
Experimental methods	Flow cytometric T-cell cytokine assay
Keywords	epitope processing, vaccine antigen design

Vaccine Details

Vaccine type	DNA prime with vaccinia boost, polyepitope
Vaccine strain	A clade, B clade, C clade
Vaccine component	Env, Gag, Nef, Pol, Vpr

Notes

• A2 mice were vaccinated with polyepitope vaccines containing 10 A2-restricted epitopes, or subsets of these epitopes, and additional alanine-augmented peptide AQMHEDIISL. Epitopes were chosen from the HIV Database Optimal Epitopes list, and were conserved among clades A, B and C.
• 3 basic constructs C1, C2, C3 were designed: C1 - epitopes linked together without flanking spacer residues; C2 - epitopes linked via spacer sequences to optimize the liberation of determinants by proteasomes; C3 - inserted flanking sequences to optimize TAP transport and, where necesary, additional residues to enhance proteasome epitope liberation. The 3 basic constructs were expressed in 3 vector plasmids: as individual sequences; as fusions with N-terminal ubiquitin (Ub); as fusions with C-terminal Ub.
• The most immunogenic construct contained N-terminal ubiquitin for targeting the polyepitope to the proteasome and included both proteasome liberation and TAP transport optimized spacer sequence that flanked the epitopes.
• This peptide was included in the constructs but did not induce response in any group of immunized animals.

References

Bazhan2010 S. I. Bazhan, L. I. Karpenko, T. N. Ilyicheva, P. A. Belavin, S. V. Seregin, N. K. Danilyuk, D. V. Antonets, and A. A. Ilyichev. Rational Design Based Synthetic Polyepitope DNA Vaccine for Eliciting HIV-Specific CD8+ T Cell Responses. Mol Immunol, 47(7-8):1507-1515, Apr 2010. PubMed ID: 20189249. Show all entries for this paper.

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Displaying record number 57827

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	IV9
Subtype	B
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, TCR binding
Keywords	rate of progression, TCR usage, optimal epitope

Notes

• The study measured the functional avidities of HIV-specific CTL responses targeting 20 optimally defined CTL epitopes in a cohort of 44 HIV controllers and 68 non-controllers. Highest functional avidities were toward HLA-B-restricted epitopes in Gag. Avidities were higher in HIV controllers than non-controllers. Higher-avidity T-cell populations had narrower TCR repertoires.
• ILKEPVHGV was one of 20 optimal epitopes tested.
• CTL response magnitude and functional avidity for this epitope did not change before and after initiation of HAART.

References

Berger2011 Christoph T. Berger, Nicole Frahm, David A. Price, Beatriz Mothe, Musie Ghebremichael, Kari L. Hartman, Leah M. Henry, Jason M. Brenchley, Laura E. Ruff, Vanessa Venturi, Florencia Pereyra, John Sidney, Alessandro Sette, Daniel C. Douek, Bruce D. Walker, Daniel E. Kaufmann, and Christian Brander. High-Functional-Avidity Cytotoxic T Lymphocyte Responses to HLA-B-Restricted Gag-Derived Epitopes Associated with Relative HIV Control. J. Virol., 85(18):9334-9345, Sep 2011. PubMed ID: 21752903. Show all entries for this paper.

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Displaying record number 62934

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HXB2 Location	Pol(464-472) RT(309-317)	Pol Epitope Map
Author Location	RT(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A2)
Immunogen	engineered, virus
Experimental methods	CTL suppression of replication
Keywords	epitope processing, viral replication, Nef-mediated down-regulation

Notes

• Nef impaired HIV-specific CTL-mediated suppression of HIV replication but this effect was ablated in IIIB-infected target T2 T cells (which are unable to present Ag on MHC Class I molecules) and with engineered CTL cell line T3F3 (which directly interacts with gp120 independent of Ag processing). Vpr did not impair CTL-mediated viral suppression.
• A2-restricted ILKEPVHGV-specific CTL clone 68A62 suppressed viral replication in target primary CD4⁺ T cells infected with NL4-3, but not in analogous cells infected with NL4-3ΔNef virus. 68A62 also suppressed viral replication in IIIB-infected T1, but not T2, T cells.
• 68A62 suppressed replication of nef-deleted HIV with or without Vpr expression in infected target T1 cells.

References

Yang2002b Otto O. Yang, Phuong Thi Nguyen, Spyros A. Kalams, Tanya Dorfman, Heinrich G. Gottlinger, Sheila Stewart, Irvin S. Y. Chen, Steven Threlkeld, and Bruce D. Walker. Nef-mediated resistance of human immunodeficiency virus type 1 to antiviral cytotoxic T lymphocytes. J Virol, 76(4):1626-31 doi, Feb 2002. PubMed ID: 11799157 Show all entries for this paper.

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Displaying record number 1595

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol(476-484)
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human(A2 supertype)
Immunogen	HIV-1 infection
Experimental methods
Keywords	supertype, rate of progression

Notes

• Long-term nonprogressors (LTNPs) had strong memory resting CD8+ T-cell responses against the majority of epitopes tested, (18 for the A2 supertype, 16 for the A3 supertype) while the effector cells of long-term nonprogressors recognized far fewer epitopes.
• Progressors had memory resting CD8+ T-cells that recognized far fewer epitopes than LTNPs.
• A positive correlation between effector CD8+ T-cells and plasma viremia and a negative correlation between CD8+ effector T-cells and CD4+ T-cells was observed, which may contribute to the inability of LTNPs to clear virus.
• This epitope can bind three of the five HLA-A2 supertypes alleles (A*0201, A*0202, A*0203, A*0206 and A*6802).

References

Propato2001 A. Propato, E. Schiaffella, E. Vicenzi, V. Francavilla, L. Baloni, M. Paroli, L. Finocchi, N. Tanigaki, S. Ghezzi, R. Ferrara, R. Chesnut, B. Livingston, A. Sette, R. Paganelli, F. Aiuti, G. Poli, and V. Barnaba. Spreading of HIV-specific CD8+ T-cell repertoire in long-term nonprogressors and its role in the control of viral load and disease activity. Hum. Immunol., 62(6):561-76, Jun 2001. PubMed ID: 11390031. Show all entries for this paper.

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Displaying record number 56510

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol
Epitope	ILKEPVHGV	Epitope Alignment
Epitope Name	Pol498
Subtype	A, B, C, D
Species (MHC/HLA)	human, mouse(A2 supertype)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	binding affinity, supertype, vaccine-induced immune responses, HLA cross-presentation

Notes

• 21 supertype-A2, -A3 and -B7-restricted epitopes predicted to be immunogenic by HLA-peptide binding motifs and phenotypic frequency in individuals were recognized by HIV-1+ subjects in ELISpot assays and shown to bind with high affinity to minimum 3 HLA-alleles of the restricting supertype. These epitopes were included in DNA vaccine EP HIV-1090 that avoided immunodominant responses and did not restrict subject immunity to predicted HLA-type when tested in mice. Transgenic mice mounted a vaccine-response similar to that induced by ELISpot assay in humans.
• Epitope ILKEPVHGV of the HLA-A2 supertype bound most strongly to HLA-A*0203, -A*6802, -A*0201 and also to -A*0202, but not to -A*0206. It was conserved 25% in subtype A, 79% in B, 88% in C and 50% in subtype D. 7/22 HLA-A2 supertype expressing HIV-1+ subjects mounted a positive ELISpot response to Pol498.

References

Wilson2003 Cara C. Wilson, Denise McKinney, Michelle Anders, Samantha MaWhinney, Jeri Forster, Claire Crimi, Scott Southwood, Alessandro Sette, Robert Chesnut, Mark J Newman, and Brian D Livingston. Development of a DNA Vaccine Designed to Induce Cytotoxic T Lymphocyte Responses to Multiple Conserved Epitopes in HIV-1. J. Immunol., 171(10):5611-5623, 15 Nov 2003. PubMed ID: 14607970. Show all entries for this paper.

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Displaying record number 55469

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	Pol
Epitope	ILKEPVHGV	Epitope Alignment
Subtype	B, C
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	Sweden
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	subtype comparisons, computational epitope prediction, vaccine antigen design

Notes

• From HIV-1 sequences of multiple subtypes, bioinformatic prediction generated 174 CTL epitopes from Gag, Pol, Nef, Env and Tat restricted by HLA supertypes A1, A2, A3, A24, B7, B44 and B58; 10 previously-published A2- and B58-restricted epitopes were also included. Of these 184 epitopes, 113 were recognized experimentally in serum from 31 HIV+ patients.
• While Gag, Pol, Env and Nef were highly immunogenic, only 38% of Tat epitopes elicited a response.
• ILKEPVHGV was a predicted epitope restricted by A2 supertype. 7/31 patient(s) responded to it; 6 were known to carry an allele of A2 supertype. Responding patients were infected with HIV clade(s) B, C.
• One of 21 epitopes denoted as elite, having a response in 4 or more of the 31 patients.

References

Perez2008 Carina L. Pérez, Mette V. Larsen, Rasmus Gustafsson, Melissa M. Norström, Ann Atlas, Douglas F. Nixon, Morten Nielsen, Ole Lund, and Annika C. Karlsson. Broadly Immunogenic HLA Class I Supertype-Restricted Elite CTL Epitopes Recognized in a Diverse Population Infected with Different HIV-1 Subtypes. J. Immunol., 180(7):5092-5100, 1 Apr 2008. PubMed ID: 18354235. Show all entries for this paper.

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Displaying record number 55096

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location
Epitope	ILKEPVHGV	Epitope Alignment
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Other
Keywords	binding affinity, acute/early infection

Notes

• Differences in early versus chronic AIDS include a decline in CTL number accompanied by a reducing viremia. Comparative analysis of such CTLs in this study show that early infection is characterized by a different clonotypic composition and higher functional avidity of CTLs followed by their selective depletion during transition to chronic disease. The total magnitude of CTL cytokine production is lower in early infection. Intraindividual, early CTLs' functional avidity for the same epitope decreases concomitantly with a reduction in clonotypic TCR repertoire especially of strongly activated and CD127lo, CD38+, Ki-67hi CTLs while progressing to chronic infection states.
• None of the target epitopes, including this epitope ILKEPVHGV seen in 1 patient, underwent sequence changes.

References

Lichterfeld2007 Mathias Lichterfeld, Xu G. Yu, Stanley K. Mui, Katie L. Williams, Alicja Trocha, Mark A. Brockman, Rachel L. Allgaier, Michael T. Waring, Tomohiko Koibuchi, Mary N. Johnston, Daniel Cohen, Todd M. Allen, Eric S. Rosenberg, Bruce D. Walker, and Marcus Altfeld. Selective Depletion of High-Avidity Human Immunodeficiency Virus Type 1 (HIV-1)-Specific CD8+ T Cells after Early HIV-1 Infection. J. Virol., 81(8):4199-4214, Apr 2007. PubMed ID: 17287271. Show all entries for this paper.

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Displaying record number 52342

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HXB2 Location	Pol(464-472) RT(309-317) DNA(3474..3500)	Pol Epitope Map
Author Location	RT(476-484 LAI)
Epitope	ILKEPVHGV	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Patient MHC/HLA	A*02:01
Experimental methods
Keywords	HAART, ART, responses in children

Notes

• Longitudinal study of 8 infants with prolonged viral suppression due to combination antiretroviral therapy showed no HIV-1 specific CTL responses in peripheral blood cells. 6/8 were studied using a Chromium release assay and no response was detected using Gag expressed in vaccinia in the target cells. Three HLA-A*0201 children were tested using SLYNTVATL or ILKEPVHGV HLA A*0201 tetramers and again no HIV-specific response was detected, either using PBMC specimens, or PBMC which had been stimulated in vitro for a week.
• In contrast, one of the children with suppressed HIV viral replication who was co-infected with HIV and EBV, while HIV-tetramer negative, had EBV-tetramer staining cells at a frequency of 0.14% in the PBMC.

References

Luzuriaga2000 Katherine Luzuriaga, Margaret McManus, Michelle Catalina, Shane Mayack, Mark Sharkey, Mario Stevenson, and John L. Sullivan. Early Therapy of Vertical Human Immunodeficiency Virus Type 1 (HIV-1) Infection: Control of Viral Replication and Absence of Persistent HIV-1-Specific Immune Responses. J. Virol., 74(15):6984-6991, Aug 2000. PubMed ID: 10888637. Show all entries for this paper.

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