Search CTL/CD8+ T-Cell Epitope Database

Found 51 matching records:

Displaying record number 58519

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(128-137)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*07)
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-B*07-restricted Nef optimal epitope TPGPGVRYPL was tested in a dual color EliSpot was 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.

Displaying record number 1057

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(128-137)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Species (MHC/HLA)	human(B*07)
Immunogen	in vitro stimulation or selection
Experimental methods
Keywords	immunodominance, dendritic cells, Th1

Notes

Dendritic cells are the most potent for priming T cell responses -- DCs can stimulate autologous CTL responses from T cells cultured from HIV negative donors.
Th1-biasing cytokines IL-12 or IFN-α enhance CTL responses in vitro whether the epitope is delivered by pulsing from peptide, or expressed from within.
CTL from a B*07 donor displayed no reactivity to this epitope, although it had been immunodominant in another study, Haas1996.

References

Haas1996 G. Haas, U. Plikat, P. Debre, M. Lucchiari, C. Katlama, Y. Dudoit, O. Bonduelle, M. Bauer, H. Ihlenfeldt, G. Jung, B. Maier, A. Meyerhans, and B. Autran. Dynamics of Viral Variants in HIV-1 Nef and Specific Cytotoxic T Lymphocytes In Vivo. J. Immunol., 157:4212-4221, 1996. PubMed ID: 8892659. Show all entries for this paper.

Wilson1999b C. C. Wilson, W. C. Olson, T. Tuting, C. R. Rinaldo, M. T. Lotze, and W. J. Storkus. HIV-1-Specific CTL Responses Primed In Vitro by Blood-Derived Dendritic Cells and Th1-Biasing Cytokines. J. Immunol., 162:3070-3078, 1999. PubMed ID: 10072560. Show all entries for this paper.

Displaying record number 1790

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(128-137)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Species (MHC/HLA)	human(B*07)
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.
Subjects with chronic HIV-1 infection recognized between 2-8 out of 11 B*07-restricted epitopes.
An acute seroconvertor homozygous for the B*07 allele recognized five B*07-restricted epitopes.
The other acute seroconvertor failed to recognize any of the 11 B*07-restricted epitopes tested.
The B*07-restricted CTL response was highly variable and there was no clearly dominant epitope.

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.

Displaying record number 53105

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(126-135)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Species (MHC/HLA)	human(B*07)
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.
6/7 patients recognized this epitope, it was the most commonly recognized of 11 B*07 epitopes.

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.

Displaying record number 59151

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef
Epitope	`TPGPGVRYPL`	Epitope Alignment
Epitope Name	TL10
Subtype	B
Species (MHC/HLA)	human(B*07)
Immunogen	HIV-1 infection
Country	Germany
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	elite controllers

Notes

In a follow-up on the anonymous 1999 Berlin patient (not Timothy Brown of 2008), viral replication suppression was seen after 15 years of absence of ART. Half the HIV-specific CTL responses in this patient were restricted by HLA-B*57, with the most immunodominant being against Nef HW9, HTQGYFPDW.
Patient autologous sequence of B*07-restricted Nef TL10, TPGPGVRYPL, elicited almost no CTL response when tested by EliSpot.

References

Jessen2014 Heiko Jessen, Todd M. Allen, and Hendrik Streeck. How a Single Patient Influenced HIV Research — 15-Year Follow-Up. N. Engl. J. Med., 370(7):682-683, 13 Feb 2014. PubMed ID: 24521131. Show all entries for this paper.

Displaying record number 1991

HXB2 Location	Nef(128-137) DNA(9178..9204)	Nef Epitope Map
Author Location	Nef
Epitope	`TPGPGVRYPL`	Epitope Alignment
Epitope Name	Nef-TL10
Subtype	B
Species (MHC/HLA)	human(B*07)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	HAART, ART

Notes

Among HIV+ individuals who carried HLA B*07, 4/9 (44%) 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.

Displaying record number 60310

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(128-137)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Epitope Name	TL10
Species (MHC/HLA)	human(B*07)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope

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.
TPGPGVRYPL had a significantly positive association with HLA B*07; it was recognized by 17/38 B*07-positive subjects and 9/303 B*07-negative subjects.

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.

Displaying record number 56405

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(128-137)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Epitope Name	TL10
Subtype	B
Species (MHC/HLA)	human(B07, B42)
Immunogen	HIV-1 infection
Country	Australia, Canada, Germany, United States
Experimental methods
Keywords	escape, HLA associated polymorphism

Notes

98 newly infected patients were studied to track early host HLA and Gag/Pol/Nef epitope immune responses' association with viral evolution. Response hierarchies were the same as those for later infection, and 50% of the most rapidly substituting epitopes were restricted by protective HLA, e.g. Gag B*57-associated mutations which were the most rapidly reverting upon transmission to a non-B*57-host. While there are great differences in mutation rates and reversions across the HIV proteome, most early viral change is driven by immune pressure.
HLA-driven epitope evolution was seen in 80% of published CTL epitopes.
HLA-B*07 and B*42-associated substitution within optimally defined epitope TPGPGVRYPL is at position V6, TPGPGvRYPL. TL10 has a 20% frequency of recognition, and escapes emerged at several time points post-infection.

References

Brumme2008 Zabrina L. Brumme, Chanson J. Brumme, Jonathan Carlson, Hendrik Streeck, Mina John, Quentin Eichbaum, Brian L Block, Brett Baker, Carl Kadie, Martin Markowitz, Heiko Jessen, Anthony D. Kelleher, Eric Rosenberg, John Kaldor, Yuko Yuki, Mary Carrington, Todd M. Allen, Simon Mallal, Marcus Altfeld, David Heckerman, and Bruce D. Walker. Marked Epitope- and Allele-Specific Differences in Rates of Mutation in Human Immunodeficiency Type 1 (HIV-1) Gag, Pol, and Nef Cytotoxic T-Lymphocyte Epitopes in Acute/Early HIV-1 Infection. J. Virol., 82(18):9216-9227, Sep 2008. PubMed ID: 18614631. Show all entries for this paper.

Displaying record number 1053

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(128-137 LAI)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*0702)
Immunogen	HIV-1 infection
Experimental methods
Keywords	optimal epitope

Notes

C. Brander notes this is a B*0702 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.

Displaying record number 54079

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	( C consensus)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*0702)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, optimal epitope

Notes

A comprehensive analysis of 160 class I T cell responses in 578 individuals from KwaZulu-Natal, South Africa was performed. Gag-specific responses were associated with lowering viremia, while Env, accessory and regulatory protein-specific responses were associated with higher viremia.
TPGPGVRYPL is an optimal epitope for B*4201 and B*0702.

References

Kiepiela2007 Photini Kiepiela, Kholiswa Ngumbela, Christina Thobakgale, Dhanwanthie Ramduth, Isobella Honeyborne, Eshia Moodley, Shabashini Reddy, Chantal de Pierres, Zenele Mncube, Nompumelelo Mkhwanazi, Karen Bishop, Mary van der Stok, Kriebashnie Nair, Nasreen Khan, Hayley Crawford, Rebecca Payne, Alasdair Leslie, Julia Prado, Andrew Prendergast, John Frater, Noel McCarthy, Christian Brander, Gerald H. Learn, David Nickle, Christine Rousseau, Hoosen Coovadia, James I. Mullins, David Heckerman, Bruce D. Walker, and Philip Goulder. CD8+ T-Cell Responses to Different HIV Proteins Have Discordant Associations with Viral Load. Nat. Med., 13(1):46-53, Jan 2007. PubMed ID: 17173051. Show all entries for this paper.

Displaying record number 57806

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef
Epitope	`TPGPGVRYPL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*0702)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	computational epitope prediction, HLA associated polymorphism

Notes

From a large study of HLA-associated polymorphisms, 431 putative epitopes with good EpiPred scores were selected; 320 of these were tested for IFNgamma EliSpot responses in subjects carrying the predicted HLA.
Peptides with response rate >40% (comparable with mean response rate of 33% for known epitopes) and tested in 5 or more individuals with respective HLA were considered in this study as probable novel epitopes and entered in the database. 41 additional "possible" novel epitopes for which either <5 individuals were tested or response rate was below 40%, are not entered in the database.
There was a markedly higher proportion of putative epitopes in Nef, and the Nef epitopes tended to have the most high-magnitude EliSpot responses. Among 33 epitopes that elicited a response in over 40% out of 5 or more individuals tested, over 61% clustered in Nef.
Epitope TPGPGVRYPL was recognized by 8/13 B*0702-positive HIV-1-infected patients.

References

Almeida2011 Coral-Ann M. Almeida, Corine Bronke, Steven G. Roberts, Elizabeth McKinnon, Niamh M. Keane, Abha Chopra, Carl Kadie, Jonathan Carlson, David W. Haas, Sharon A. Riddler, Richard Haubrich, David Heckerman, Simon Mallal, and Mina John. Translation of HLA-HIV Associations to the Cellular Level: HIV Adapts to Inflate CD8 T Cell Responses against Nef and HLA-Adapted Variant Epitopes. J. Immunol., 187(5):2502-2513, 1 Sep 2011. PubMed ID: 21821798. Show all entries for this paper.

Displaying record number 57994

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location
Epitope	`TPGPGVRYPL`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*0702)
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.
TPGPGVRYPL was predicted from EliSpot-positive 18mer NYTPGPGVRYPLTFGWCF. The epitope was validated in one B*0702-positive HIV-positive individual 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.

Displaying record number 1829

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(128-137 LAI)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*0702)
Immunogen	in vitro stimulation or selection
Experimental methods
Keywords	epitope processing

Notes

Five naturally processed MHC class I ligands were identified in Nef in the conserved immunogenic region Nef between 123-152.
All five could be transported by TAP, and 4/5 had N-termini that were major cleavage points for the proteasome, only one had extended precursor fragments.
Both TPGPGVRYPL and TPGPGVRY are naturally processed ligands that can be eluted from HLA-B7 molecules, both are recognized by the same CTL, and both peptides seem to be the direct product of a proteasomal digest.
The peptide TPGPGVRY is present in a high copy number, TPGPGVRYPL at a more moderate level, possibly due to a major cleavage site between the Y and P.

References

LucchiariHartz2000 M. Lucchiari-Hartz, P. M. van Endert, G. Lauvau, R. Maier, A. Meyerhans, D. Mann, K. Eichmann, and G. Niedermann. Cytotoxic T lymphocyte epitopes of HIV-1 Nef: Generation of multiple definitive major histocompatibility complex class I ligands by proteasomes. J. Exp. Med., 191(2):239-52, 17 Jan 2000. URL: http://www.jem.org/cgi/content/full/191/2/239. PubMed ID: 10637269. Show all entries for this paper.

Displaying record number 58863

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(128-137)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Epitope Name	TL10
Subtype	B
Species (MHC/HLA)	human(B*0702)
Immunogen	HIV-1 infection
Country	Australia
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	escape, optimal epitope, HLA associated polymorphism

Notes

Epitopes that have undergone escape are often still immunogenic. Scanning for epitopes that encompass HLA-specific polymorphisms revealed 97 HLA-polymorphism associations in which the mutation resulted in the creation rather than abolition of an epitope, termed a "neo-epitope". This study examined 9 neo-epitopes that were well-characterized optimal epitopes that elicit T-cell responses in chronic infection. HIV-1 adaptation not only abrogates the immune recognition of early targeted epitopes, but may also increase immune recognition to other epitopes, which elicit immunodominant but non-protective T-cell responses.
Neo-epitope TPGPGVRYPL underwent adaptation from TPGPGIRYPL. 6 subjects had higher EliSpot responses to the neo-epitope than to the non-adapted form.
HLA-B*0702-expressing PBMCs from 2 individuals were cultured with TL10 adapted and non-adapted epitopes to generate epitope-specific T-cell lines. The frequencies of central memory and effector memory T cells were not significantly different whether directed against non-adapted or adapted epitopes.
No difference was found in TCR expression between epitope-specific CTLs from adapted and non-adapted forms of this epitope, TL10.

References

Keane2012 Niamh M. Keane, Steven G. Roberts, Coral-Ann M. Almeida, Tanya Krishnan, Abha Chopra, Emma Demaine, Rebecca Laird, Monika Tschochner, Jonathan M. Carlson, Simon Mallal, David Heckerman, Ian James, and Mina John. High-Avidity, High-IFN-gamma-Producing CD8 T-Cell Responses following Immune Selection during HIV-1 Infection. Immunol. Cell Biol., 90(2):224-234, Feb 2012. PubMed ID: 21577229. Show all entries for this paper.

Displaying record number 53301

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	( C consensus)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B0702, B4201)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	HLA cross-presentation, characterizing CD8+ T cells

Notes

HLA class I restricted CD8+ T-cell responses against HIV-1 were analyzed in African patients. Significantly more responses were shown to be HLA-B restricted. Viral load, CD4 count, and thus rate of disease progression were also associated with HLA-B alleles. In addition, the selection pressure imposed on HIV-1 by HLA-B alleles was shown to be substantially greater than by other alleles.
This epitope was suggested to be the epitope within a longer reactive peptide based on correspondence with a known epitope in the HIV database. Also, a significantly higher frequency of people in the Durban cohort who reacted with the peptide had this HLA type.

References

Kiepiela2004 Photini Kiepiela, Alasdair J. Leslie, Isobella Honeyborne, Danni Ramduth, Christina Thobakgale, Senica Chetty, Prinisha Rathnavalu, Corey Moore, Katja J. Pfafferott, Louise Hilton, Peter Zimbwa, Sarah Moore, Todd Allen, Christian Brander, Marylyn M. Addo, Marcus Altfeld, Ian James, Simon Mallal, Michael Bunce, Linda D. Barber, James Szinger, Cheryl Day, Paul Klenerman, James Mullins, Bette Korber, Hoosen M. Coovadia, Bruce D. Walker, and Philip J. R. Goulder. Dominant Influence of HLA-B in Mediating the Potential Co-Evolution of HIV and HLA. Nature, 432(7018):769-775, 9 Dec 2004. LA-UR 04-5920. PubMed ID: 15592417. Show all entries for this paper.

Displaying record number 56234

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location
Epitope	`TPGPGVRYPL`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*0702, B7)
Immunogen	HIV-1 infection
Patient MHC/HLA	A3204, A7412, B0702, B4403, Cw0210, Cw0702
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay
Keywords	rate of progression, immunodominance

Notes

47 HIV-1 subtype C infected patients were followed longitudinally to determine whether there was a relation between magnitude and breadth of CTL responses in primary, acute infection (measured by IFN-gamma ELISpot) and disease progression (measured as viral load at 12 months). CTL responses to Nef were dominant (targeting 6 epitopic regions), followed by responses to Gag, Pol, Rev, Vpr, Env, Vpu, Vif and finally Tat.
TPGPGVRYPL is a known HLA-B7/-B*0702-restricted epitope that is part of peptide PGPGVRYPLTFGWCFKLVP which elicited the most dominant response in 8/10 patients. Response to a peptide containing this epitope was detected in 1 rapid progressor 12 weeks post-infection.

References

Gray2009 Clive M. Gray, Mandla Mlotshwa, Catherine Riou, Tiyani Mathebula, Debra de Assis Rosa, Tumelo Mashishi, Cathal Seoighe, Nobubelo Ngandu, Francois van Loggerenberg, Lynn Morris, Koleka Mlisana, Carolyn Williamson, Salim Abdool Karim, and CAPRISA 002 Acute Infection Study Team. Human Immunodeficiency Virus-Specific gamma Interferon Enzyme-Linked Immunospot Assay Responses Targeting Specific Regions of the Proteome during Primary Subtype C Infection Are Poor Predictors of the Course of Viremia and Set Point. J. Virol., 83(1):470-478, Jan 2009. PubMed ID: 18945774. Show all entries for this paper.

Displaying record number 61013

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(128-137)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 infection
Patient MHC/HLA	41325: A2902, A3201, B3501, B4403, Cw0401, Cw1601; 57604: A0201, A0201, B1302, B3501, Cw0419, Cw0602
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	acute/early infection

Notes

The extent to which set-point viremia is affected by early HIV-infection T cell responses to either conserved or variable epitopes was studied. 23 ART-naive subjects were characterized for CTL responses for 6 months, postinfection. While most CTL responses (73/123) were targeted against variable HIV-1 epitopes, recognition of conserved epitopes (16/123) was associated with lower set point viremia. This was independent of HLA type and also functional avidity of the CTL response. Most of the conserved responses were targeted to Gag and Pol epitopes.
TPGPGVRYPL, restricted by B35, was recognized by 2 patients with the restricting allele.

References

Kunwar2013 Pratima Kunwar, Natalie Hawkins, Warren L. Dinges, Yi Liu, Erin E. Gabriel, David A. Swan, Claire E. Stevens, Janine Maenza, Ann C. Collier, James I. Mullins, Tomer Hertz, Xuesong Yu, and Helen Horton. Superior Control of HIV-1 Replication by CD8+ T Cells Targeting Conserved Epitopes: Implications for HIV Vaccine Design. PLoS One, 8(5):e64405, 2013. PubMed ID: 23741326. Show all entries for this paper.

Displaying record number 52130

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(128-137 BRU)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 infection
Experimental methods
Keywords	binding affinity, epitope processing

Notes

Seventy-three 8-11 mer peptides were generated based on putative anchor motifs in the Nef BRU sequence for HLA A2, A3, A24, B7, B8, and B35; these 73 peptides had 81 motifs. 54% bound to the predicted HLA molecule, particularly A2, B7/35, and B8. The strength of HLA-peptide binding was not directly related to the number of individuals that recognized a protein.
20s proteasome cleavage of the Nef protein positions 66-100 showed a large fraction of peptides were cleaved ending at: 87L, 83A, 81Y, 71P, 68F and 67G. The frequency of recognition may be in part dictated by the cleavage step in processing.
TPGPGVRYPL was recognized in 8/16 (50%) of individuals with HLA B7, and 1/9 (11%) of individuals with HLA B35. It was a high affinity HLA binder.

References

Choppin2001 Jeannine Choppin, William Cohen, Albert Bianco, Jean-Paul Briand, Francine Connan, Marc Dalod, and Jean-Gérard Guillet. Characteristics of HIV-1 Nef Regions Containing Multiple CD8+ T Cell Epitopes: Wealth of HLA-Binding Motifs and Sensitivity to Proteasome Degradation. J. Immunol., 166(10):6164-6169, 15 May 2001. PubMed ID: 11342637. Show all entries for this paper.

Displaying record number 60312

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(128-137)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Epitope Name	TL10
Species (MHC/HLA)	human(B3502, B3503, B*5301)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope

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.
TPGPGVRYPL had a significantly positive association with HLA B*3502,B*3503,B*5301; it was recognized by 4/34 B*3502,B*3503,B*5301-positive subjects and 1/254 B*3502,B*3503,B*5301-negative subjects.

References

Displaying record number 53829

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(128-137)
Epitope	`TPGPGVRYPL`	Epitope Alignment
		Show epitope variants
Subtype	C
Species (MHC/HLA)	human(B*4201)
Immunogen	HIV-1 infection
Patient MHC/HLA	A30, A3001, B1503, B4201, Cw0202, Cw1701; A0301, A3001, B4201, B5802, Cw0602, Cw1701
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	responses in children, mother-to-infant transmission, escape, acute/early infection

Notes

HIV-specific CTLs in infants were shown to be able to select for viral escape variants early in life, despite a lack of escape with the same CTL specificity in the mother. Infant CTL responses may be compromised by transmission of escape variants that arose in the mother and also those that arose in the father, if the father was the source of the mother's infection.
Escape variants tSgpgvrypl and tQgpgvrypl were rapidly selected in an infant, by 26 weeks, but were not found in the infant's mother. These forms were demonstrated to be escape mutations by Elispot, and also had reduced binding to B*4201 in a competitive inhibition assay.

References

Pillay2005 Thillagavathie Pillay, Hua-Tang Zhang, Jan W. Drijfhout, Nicola Robinson, Helen Brown, Munira Khan, Jagadesa Moodley, Miriam Adhikari, Katja Pfafferott, Margaret E. Feeney, Anne St. John, Edward C. Holmes, Hoosen M. Coovadia, Paul Klenerman, Philip J. R. Goulder, and Rodney E. Phillips. Unique Acquisition of Cytotoxic T-Lymphocyte Escape Mutants in Infant Human Immunodeficiency Virus Type 1 Infection. J. Virol., 79(18):12100-12105, Sep 2005. PubMed ID: 16140787. Show all entries for this paper.

Displaying record number 59445

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(382-411)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Epitope Name	Nef-TL10
Subtype	C
Species (MHC/HLA)	human(B*4201)
Immunogen	HIV-1 infection
Country	Botswana, South Africa, United Kingdom
Experimental methods	CD8 T-cell Elispot - IFNγ, Other, Tetramer binding
Keywords	immunodominance

Notes

2,093 HLA-B*4201⁺ ART-naive female adults from 5 cohorts with chronic C-clade infection were studied to determine factors controlling immunodominance. Immunodominant hierarchy of response observed across 20 HLA-B*4201-restricted epitopes was not linked to peptide-B*4201 binding affinity or stability. Immunodominance correlated instead with the particular amino acid residues within (TCRβ) TRB sequences. Extreme TCR biases towards generating identical or 'public' epitope-specific TCRs in multiple individuals therefore were statistically the greatest influence upon Immunodomination.
13 B*4201⁺-restricted novel epitopes were identified by EliSpot screening of 181 females with 410 HIV-1 OLPs.
11 different public clonotypes were identified and were used by the top 3 ranked immunodominant epitope-specificities.
6/10 most immunodominant epitopes were Gag/Pol/Vpr-specific and 100% showed selection pressure on HIV. Of 4 epitopes that were Nef/Vif-specific and among most immunodominant, only 25% i.e one epitope experienced selection pressure in the virus.
Epitope TPGPGVRYPL from OLP Nef-84 (NYTPGPGVRYPLTFGWCF) had a targeting frequency of ˜41% of 154 HLA-B*4201⁺ subjects. Immunodominance rank was 5/20 tested epitopes.
Nef-TL10-HLA-B*4202's binding affinity, K_d = 1 nM; stability, K_1/2 = 14.3h.

References

Kloverpris2015 Henrik N Kløverpris, Reuben McGregor, James E. McLaren, Kristin Ladell, Mikkel Harndahl, Anette Stryhn, Jonathan M. Carlson, Catherine Koofhethile, Bram Gerritsen, Can Keşmir, Fabian Chen, Lynn Riddell, Graz Luzzi, Alasdair Leslie, Bruce D. Walker, Thumbi Ndung'u, Søren Buus, David A. Price, and Philip J. Goulder. CD8+ TCR Bias and Immunodominance in HIV-1 Infection. J. Immunol., 194(11):5329-5345, 1 Jun 2015. PubMed ID: 25911754. Show all entries for this paper.

Displaying record number 55174

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location
Epitope	`TPGPGVRYPL`	Epitope Alignment
Epitope Name	TL10
Species (MHC/HLA)	human(B*4201)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	Intracellular cytokine staining, Proliferation, Tetramer binding
Keywords

Notes

PD-1 (inhibitory receptor programmed death) expression on CD8 and CD4 cells was studied. There was a positive correlation with viral load and inverse correlation with CD4 T cell count, and blockage of PD-1 pathway augmented CD4 and CD8 T cell function.

References

Day2006 Cheryl L. Day, Daniel E. Kaufmann, Photini Kiepiela, Julia A. Brown, Eshia S. Moodley, Sharon Reddy, Elizabeth W. Mackey, Joseph D. Miller, Alasdair J. Leslie, Chantal DePierres, Zenele Mncube, Jaikumar Duraiswamy, Baogong Zhu, Quentin Eichbaum, Marcus Altfeld, E. John Wherry, Hoosen M. Coovadia, Philip J. R. Goulder, Paul Klenerman, Rafi Ahmed, Gordon J. Freeman, and Bruce D. Walker. PD-1 Expression on HIV-Specific T Cells Is Associated with T-Cell Exhaustion and Disease Progression. Nature, 443(7109):350-354, 21 Sep 2006. PubMed ID: 16921384. Show all entries for this paper.

Displaying record number 1058

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(128-137 LAI)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*4201)
Immunogen
Experimental methods
Keywords	optimal epitope

Notes

C. Brander notes this is a B*4201 epitope.

References

Displaying record number 59161

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(128-137)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Epitope Name	TL10-Nef
Subtype	C
Species (MHC/HLA)	human(B*4201)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding, Tetramer binding
Keywords	TCR usage, characterizing CD8+ T cells

Notes

Inhibitory receptor [programmed death-1 (PD-1)/lymphocyte activation gene-3 (LAG-3)/ T-cell immunoglobulin and mucin domain-3 (Tim-3)] expression was studied during chronic infection in 128 CTL populations from 32 ART-naive, sub-Saharan, HIV-clade C-infected subjects expressing either HLA-B*1503 or -B*4201. PD-1 was found to vary across epitope specificity whether inter- or intra-subject. PD-1 also varied with different TCR clonotypes even within one HIV-specific CTL population. PD-1 correlates directly with viral load (VL).
CTL specific for TL10-Nef, TPGPGVRYPL, a low variable epitope, were found to have significant correlation with VL.

References

Kloverpris2014a Henrik N. Kløverpris, Reuben McGregor, James E McLaren, Kristin Ladell, Anette Stryhn, Catherine Koofhethile, Jacqui Brener, Fabian Chen, Lynn Riddell, Luzzi Graziano, Paul Klenerman, Alasdair Leslie, Søren Buus, David A. Price, and Philip Goulder. Programmed Death-1 Expression on HIV-1-Specific CD8+ T Cells Is Shaped by Epitope Specificity, T-Cell Receptor Clonotype Usage and Antigen Load. AIDS, 28(14):2007-2021, 10 Sep 2014. PubMed ID: 24906112. Show all entries for this paper.

Displaying record number 54078

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	( C consensus)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*4201)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, optimal epitope

Notes

A comprehensive analysis of 160 class I T cell responses in 578 individuals from KwaZulu-Natal, South Africa was performed. Gag-specific responses were associated with lowering viremia, while Env, accessory and regulatory protein-specific responses were associated with higher viremia.
TPGPGVRYPL is an optimal epitope for B*4201 and B*0702.

References

Displaying record number 58719

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(128-137)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Epitope Name	Nef-TL10
Subtype	C
Species (MHC/HLA)	human(B4201, B4202)
Immunogen	HIV-1 infection
Patient MHC/HLA	A3001, B4201, Cw1701; A3001, B4202, Cw1701
Country	Botswana, South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding, Tetramer binding
Keywords	HLA associated polymorphism, novel epitope

Notes

Using an outbred cohort of 2,093 clade-C-infected southern African subjects who carry the HLA-B*42 allele, the authors determine that a single amino acid change between B*4202 and B*4201 is responsible for the difference in HLA-B*4201 presenting multiple Gag epitopes with a lower VL; and HLA-B*0402 which presents no p24 Gag epitopes. Thus a single nucleotide polymorphism (SNP) on the HLA class I locus is associated with significant differences in HIV disease control.
While no substantial difference was seen in the peptide binding motifs of both HLAs, as well as no overall difference in targeting of Pol, Nef or Env epitopes, a significantly larger number of HLA-B*4201-positive subjects recognized Gag epitopes.
Nef epitope TL10, TPGPGVRYPL, was recognized by > 40% of Nef/Vpr/Vif/Env/Pol HLA-B*4201- and by > 80% B*4202-positive responders, although the half life of TL10 binding both B*4201 and B*4202 were similar. This is the first report of TPGPGVRYPL as restricted by HLA-B*4202.

References

Kloverpris2012a Henrik N. Kløverpris, Mikkel Harndahl, Alasdair J. Leslie, Jonathan M. Carlson, Nasreen Ismail, Mary van der Stok, Kuan-Hsiang Gary Huang, Fabian Chen, Lynn Riddell, Dewald Steyn, Dominique Goedhals, Cloete van Vuuren, John Frater, Bruce D. Walker, Mary Carrington, Thumbi Ndung'u, Søren Buus, and Philip Goulder. HIV Control through a Single Nucleotide on the HLA-B Locus. J. Virol., 86(21):11493-11500, Nov 2012. PubMed ID: 22896606. Show all entries for this paper.

Displaying record number 58628

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location
Epitope	`TPGPGVRYPL`	Epitope Alignment
Species (MHC/HLA)	(B*4202)
Immunogen
Experimental methods
Keywords	optimal epitope

Notes

C. Brander noted this as an optimal B*4202 epitope based on data from Kloverpris JV 2012.

References

Displaying record number 53403

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef
Epitope	`TPGPGVRYPL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B7)
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.

Displaying record number 1051

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location
Epitope	`TPGPGVRYPL`	Epitope Alignment
Species (MHC/HLA)	human(B7)
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 there was a close temporal relationship between the number of circulating HIV-specific T cells and viral load was also found.
All three patients were B*2705, with HLA alleles: A1, A30/31, B*2705, B35; A1, A*0301, B7, B*2705; and A*0201, A*0301, B*2705, 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.

Displaying record number 1052

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(128-137 LAI)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

There was a high degree of variation in three CTL epitopes in Nef in four slow and non-progressors, and variant specific CTLs arose over time to eliminate variants, indicating immune selection.
The epitope position was taken from <cite>Haas1997</cite>

References

Haas1997 G. Haas, A. Hosmalin, F. Hadida, J. Duntze, P. Debre, and B. Autran. Dynamics of HIV Variants and Specific Cytotoxic T Cell Recognition in Nonprogressors and Progressors. Immunol. Lett., 57:63-68, 1997. PubMed ID: 9232427. Show all entries for this paper.

Displaying record number 1054

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef
Epitope	`TPGPGVRYPL`	Epitope Alignment
		Show epitope variants
Species (MHC/HLA)	human(B7)
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 D subtype consensus is identical to the B clade epitope.
The A subtype consensus is TPGPGIRYPL.

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.

Displaying record number 1056

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef( subtype B)
Epitope	`TPGPGVRYPL`	Epitope Alignment
		Show epitope variants
Subtype	B
Species (MHC/HLA)	human(B7)
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.
The Clade A version of the epitope: TPGPGIRYPL.

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.

Displaying record number 1573

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(128-137 SF2)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Species (MHC/HLA)	human(B7)
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-B7+ individuals that had a CTL response to this epitope broken down by group: 0/4 group 1, 0/3 group 2, and 1/1 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.

Displaying record number 1669

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(128-137)
Epitope	`TPGPGVRYPL`	Epitope Alignment
		Show epitope variants
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 exposed seronegative, HIV-1 infection
Experimental methods
Keywords	HIV exposed persistently seronegative (HEPS), immunodominance

Notes

ELISPOT was used to study CTL responses to a panel of 54 predefined HIV-1 epitopes in 91 HIV-1-exposed, persistently seronegative (HEPS) and 87 HIV-1-infected female Nairobi sex workers.
Responses in HEPS women tended to be lower, and focused on different epitopes with HLA presenting molecules that have previously been associated with reduced risk of infection, and there was a shift in the response in the HEPS women upon late seroconversion to epitopes recognized by the HIV-1 infected women.
43/91 HEPS women had CD8+ responses and detection of HIV-1-specific CTL in HEPS women increased with the duration of viral exposure.
Among HLA-B7 women, 4/5 HEPS and 5/6 HIV-1 infected women recognized this epitope.
The dominant response to this HLA allele was to this epitope in 3 of the 4/5 HEPS cases and in 2 of the 5/6 HIV-1 infected women.
Subject ML 1203 started with CTL responses to A*6802 DTVLEDINL and to B7 FPVTPQVPLR prior to seroconversion, and upon seroconversion acquired additional responses to A*6802 ETAYFILKL which became dominant, B7 TPGPG(V/I)RYPL, B7 IPRRIRQGL, and B7 SPRTLNAWV.

References

Kaul2001a R. Kaul, T. Dong, F. A. Plummer, J. Kimani, T. Rostron, P. Kiama, E. Njagi, E. Irungu, B. Farah, J. Oyugi, R. Chakraborty, K. S. MacDonald, J. J. Bwayo, A. McMichael, and S. L. Rowland-Jones. CD8(+) lymphocytes respond to different HIV epitopes in seronegative and infected subjects. J. Clin. Invest., 107(10):1303-10, May 2001. URL: http://www.jci.org/cgi/content/full/107/10/1303. PubMed ID: 11375420. Show all entries for this paper.

Displaying record number 1704

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(128-137)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Species (MHC/HLA)	human(B7)
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.

Displaying record number 52129

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(128-137 BRU)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Experimental methods
Keywords	binding affinity, epitope processing

Notes

Seventy-three 8-11 mer peptides were generated based on putative anchor motifs in the Nef BRU sequence for HLA A2, A3, A24, B7, B8, and B35; these 73 peptides had 81 motifs. 54% bound to the predicted HLA molecule, particularly A2, B7/35, and B8. The strength of HLA-peptide binding was not directly related to the number of individuals that recognized a protein.
20s proteasome cleavage of the Nef protein positions 66-100 showed a large fraction of peptides were cleaved ending at: 87L, 83A, 81Y, 71P, 68F and 67G. The frequency of recognition may be in part dictated by the cleavage step in processing.
TPGPGVRYPL was recognized in 8/16 (50%) of individuals with HLA B7, and 1/9 (11%) of individuals with HLA B35. It was a high affinity HLA binder.

References

Displaying record number 52170

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef
Epitope	`TPGPGVRYPL`	Epitope Alignment
Epitope Name	B7-TL10
Subtype	B
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Patient MHC/HLA	A3, B7, Cw7
Experimental methods
Keywords	dynamics, supervised treatment interruptions (STI), acute/early infection

Notes

CTL responses in 18 acutely HIV-infected HLA-A3 (n=7) or -B7 (n=4) or both -A3 and B7 (n=7) positive individuals were studied.
One individual, AC-06, was homozygous at all three class I alleles (A3, B7, Cw7), was treated during acute infection and had supervised treatment interruptions (STI). He had only two detectable CTL responses during acute infection, but after STI this broadened to 27 distinct epitopes including 15 restricted by HLA-A3, 11 by HLA-B7, and 1 by HLA-Cw7.
0/11 HLA-B7 individuals had detectable B7-restricted responses to this epitope during acute infection -- 10/15 of HLA-B7 epitopes tested were targeted by at least one person during acute infection. 2/4 individuals had detectable responses to this epitope after STI.

References

Yu2002b Xu G. Yu, Marylyn M. Addo, Eric S. Rosenberg, William R. Rodriguez, Paul K. Lee, Cecily A. Fitzpatrick, Mary N. Johnston, Daryld. Strick, Philip J. R. Goulder, Bruce D. Walker, and Marcus Altfeld. Consistent Patterns in the Development and Immunodominance of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific CD8+ T-Cell Responses Following Acute HIV-1 Infection. J. Virol., 76(17):8690-8701, Sep 2002. PubMed ID: 12163589. Show all entries for this paper.

Displaying record number 52360

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef
Epitope	`TPGPGVRYPL`	Epitope Alignment
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Patient MHC/HLA	A2, A3, B7, Bw6
Experimental methods
Keywords	HAART, ART

Notes

Four HIV patients with prolonged clinically successful anti-viral therapy but with ongoing evidence of replication and Nef mRNA transcription, showed specific T-cell responses by Elispot and Tetramer staining, maintained for 2-4 years after initiation of HAART.
Nef epitope recognition was detected in all 4 subjects, gp120, Pol and Gag-specific in 1 or 2 subjects.
The HIV-specific CD8+ T-cells had an intermediate maturation phenotype characterized by low levels of perforin and high levels of CD27 expression.

References

Appay2002 Victor Appay, Pokrath Hansasuta, Julian Sutton, Rachel D. Schrier, Joseph K. Wong, Manohar Furtado, Diane V. Havlir, Steven M. Wolinsky, Andrew J. McMichael, Douglas D. Richman, Sarah L. Rowland-Jones, and Celsa A. Spina. Persistent HIV-1-Specific Cellular Responses Despite Prolonged Therapeutic Viral Suppression. AIDS, 16(2):161-170, 25 Jan 2002. PubMed ID: 11807299. Show all entries for this paper.

Displaying record number 52443

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef
Epitope	`TPGPGVRYPL`	Epitope Alignment
Subtype	B, C
Species (MHC/HLA)	human, macaque(B7)
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.

Displaying record number 53040

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef
Epitope	`TPGPGVRYPL`	Epitope Alignment
Species (MHC/HLA)	human(B7)
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.
No one, 0/9 HLA B7+ infection-resistant men, and 0/4 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.

Displaying record number 53383

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	( B consensus)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Epitope Name	TL10
Subtype	B
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Patient MHC/HLA	A31, A68, B7, B70, Cw1, 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.

Displaying record number 55033

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location
Epitope	`TPGPGVRYPL`	Epitope Alignment
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding
Keywords	binding affinity, immunodominance, optimal epitope

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 TPGPGVRYPL elicited a magnitude of response of 210 SFC with a functional avidity of 0.5nM and binding affinity of 5.1nM.

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.

Displaying record number 55491

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef
Epitope	`TPGPGVRYPL`	Epitope Alignment
Epitope Name	TL10
Subtype	B
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay, Tetramer binding
Keywords	superinfection

Notes

Loss of viral replication control by an elite controller after superinfection was found to coincide with rapid recombination events in 2, ~50 residue regions of Gag and Env that include immunodominant epitopes KK10 (KRWIILGLNK) and CL9 (CAPAGFAIL). Viral escape was seen at both epitopes and consequent CTL responses against the epitope-variants.
CTL responses to previously described, HLA-B7-restricted TPGPGVRYPL were seen post-superinfection and -recombination.

References

Streeck2008a Hendrik Streeck, Bin Li, Art F. Y. Poon, Arne Schneidewind, Adrianne D. Gladden, Karen A. Power, Demetre Daskalakis, Suzane Bazner, Rosario Zuniga, Christian Brander, Eric S. Rosenberg, Simon D. W. Frost, Marcus Altfeld, and Todd M. Allen. Immune-Driven Recombination and Loss of Control after HIV Superinfection. J. Exp. Med., 205(8):1789-1796, 4 Aug 2008. PubMed ID: 18625749. Show all entries for this paper.

Displaying record number 57175

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location
Epitope	`TPGPGVRYPL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	acute/early infection

Notes

To compare the prevalence and immunodominance of CTL responses to conserved and variable epitopes, CTL responses were analyzed in 45 HIV-1 B-infected males during primary and/or chronic infection. Conserved and variable CTL epitopes were recognized with similar probabilities, but conserved epitopes generally elicited subdominant responses. Low viral loads were associated with Gag-specific responses during acute infection, but with Env-specific responses during chronic infection.
Among 5 B7-positive subjects tested during chronic infection, 3 recognized TPGPGVRYPL, and none had an immunodominant response to it.

References

Liu2009c Yi Liu, John McNevin, Morgane Rolland, Hong Zhao, Wenjie Deng, Janine Maenza, Claire E. Stevens, Ann C. Collier, M. Juliana McElrath, and James I. Mullins. Conserved HIV-1 Epitopes Continuously Elicit Subdominant Cytotoxic T-Lymphocyte Responses. J. Infect. Dis., 200(12):1825-1833, 15 Dec 2009. PubMed ID: 19909083. Show all entries for this paper.

Displaying record number 57831

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef
Epitope	`TPGPGVRYPL`	Epitope Alignment
Epitope Name	TL10
Subtype	B
Species (MHC/HLA)	human(B7)
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.
TPGPGVRYPL was one of 20 optimal epitopes tested.

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.

Displaying record number 1050

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(128-137 subtype B)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*8101, B7)
Immunogen	HIV-1 exposed seronegative
Experimental methods
Keywords

Notes

11/16 heavily HIV exposed but persistently seronegative sex-workers in Nairobi had HIV-specific CD8 gamma-IFN responses in the cervix -- systemic CD8+ T cell responses tended to be to the same epitopes but at generally lower levels than cervical CD8+ T cell responses.
Low risk individuals did not have such CD8+ cells.
CD8+ T cell epitopes: DTVLEDINL (3 individuals), SLYNTVATL (4 individuals), LSPRTLNAW (3 individuals) and YPLTFGWCF (4 individuals) were most commonly recognized by the HIV-resistant women.

References

Kaul2000 R. Kaul, F. A. Plummer, J. Kimani, T. Dong, P. Kiama, T. Rostron, E. Njagi, K. S. MacDonald, J. J. Bwayo, A. J. McMichael, and S. L. Rowland-Jones. HIV-1-Specific Mucosal CD8+ Lymphocyte Responses in the Cervix of HIV-1-Resistant Prostitutes in Nairobi. J. Immunol., 164:1602-1611, 2000. PubMed ID: 10640781. Show all entries for this paper.

Displaying record number 1055

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef( subtype B)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*8101, B7)
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.
Clade A version of the epitope: TPGPGIRYPL, clade D version: TPGPGIRYPL.

References

Displaying record number 52962

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(128-137)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B7 supertype)
Immunogen	vaccine
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, Proliferation
Keywords	vaccine-induced immune responses, variant cross-reactivity

Vaccine Details

Vaccine type	lipopeptide
Vaccine strain	B clade LAI
Vaccine component	Env, Gag, Nef
Adjuvant	QS21

Notes

After injection of an anti-HIV-1 lipopeptide vaccine and the booster injections, a response was observed in >85% of 28 volunteers, and a long-term immune response was observed in >50% of the volunteers. A positive effect of QS21 adjuvant was found for B-and CD4+T-cell responses. A higher number of CD8+ T-cell epitopes was induced after a fourth boost injection. This epitope was one of the 31 epitopes that the vaccinated volunteers responded to.

References

Gahery-Segard2003 Hanne Gahéry-Ségard, Gilles Pialoux, Suzanne Figueiredo, Céline Igéa, Mathieu Surenaud, Jessintha Gaston, Helene Gras-Masse, Jean-Paul Lévy, and Jean-Gérard Guillet. Long-Term Specific Immune Responses Induced in Humans by a Human Immunodeficiency Virus Type 1 Lipopeptide Vaccine: Characterization of CD8+-T-Cell Epitopes Recognized. J. Virol., 77(20):11220-11231, Oct 2003. PubMed ID: 14512570. Show all entries for this paper.

Displaying record number 57762

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef
Epitope	`TPGPGVRYPL`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*8101)
Immunogen	HIV-1 infection
Patient MHC/HLA	A0101, A3001, B4202, B8101, Cw1701, Cw1801
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, acute/early infection

Notes

Immunological responses in early subtype C infection were characterized. Nef, Pol and Gag were the most frequently targeted proteins from as early as 3 to 8 weeks postinfection. Nef was immunodominant, with more than 75% of individuals recognizing Nef. Many responses to peptide pools were derived from the recognition of one immunodominant peptide.
One B*8101-positive acutely HIV-1-infected individual had a peptide response to presumed optimal epitope TPGPGVRYPL within peptide QNYTPGPGVRYPLTF. Autologous viral escape occurred in 1.5 weeks, and response was lost at 29 weeks.

References

Mlotshwa2010 Mandla Mlotshwa, Catherine Riou, Denis Chopera, Debra de Assis Rosa, Roman Ntale, Florette Treunicht, Zenda Woodman, Lise Werner, Francois van Loggerenberg, Koleka Mlisana, Salim Abdool Karim, Carolyn Williamson, Clive M Gray, and CAPRISA 002 Study Team. Fluidity of HIV-1-Specific T-Cell Responses during Acute and Early Subtype C HIV-1 Infection and Associations with Early Disease Progression. J. Virol., 84(22):12018-12029, Nov 2010. PubMed ID: 20826686. Show all entries for this paper.

Displaying record number 60311

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(128-137)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Epitope Name	TL10
Species (MHC/HLA)	human(C*17)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope

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.
TPGPGVRYPL had a significantly positive association with HLA C*17; it was recognized by 4/15 C*17-positive subjects and 5/288 C*17-negative subjects.

References

Displaying record number 54195

HXB2 Location	Nef(128-137) DNA(9178..9207)	Nef Epitope Map
Author Location	Nef(128-137)
Epitope	`TPGPGVRYPL`	Epitope Alignment
Epitope Name	TL10
Subtype	C
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, Other, Tetramer binding
Keywords	supertype, HLA cross-presentation, TCR usage, HLA associated polymorphism

Notes

14 promiscuous HIV-specific CTL epitopes presented by B7 supertype alleles were described. It was shown that CTLs targeting an identical epitope that are restricted by closely related but different HLA alelles differ in several ways: by occurrence of distinct HLA-specific escape mutations, by recruitment of distinct TCRs by peptide/MHC complexes, and by functional avidity of CTLs. Since there were no differences in the frequency, magnitude or immunodominance of the CTL responses restricted by different HLA alleles, it is suggested that the unique peptide/MHC complexes generated by closely related HLA induce qualitatively different CTL responses.
Functional avidity is correlated with selection pressure observed in HLA allele-epitope restriction
Statistically significant associations between numbers of HLA-0702 and -B4201 expressing subjects and epitope TPGPGVRYPL were found.
Only B*0702 was found to be associated with polymorphism in TL10.

References

Leslie2006 Alasdair Leslie, David A. Price, Pamela Mkhize, Karen Bishop, Almas Rathod, Cheryl Day, Hayley Crawford, Isobella Honeyborne, Tedi E. Asher, Graz Luzzi, Anne Edwards, Christine M. Rousseau, James I. Mullins, Gareth Tudor-Williams, Vas Novelli, Christian Brander, Daniel C. Douek, Photini Kiepiela, Bruce D. Walker, and Philip J. R. Goulder. Differential Selection Pressure Exerted on HIV by CTL Targeting Identical Epitopes but Restricted by Distinct HLA Alleles from the Same HLA Supertype. J. Immunol., 177(7):4699-4708, 1 Oct 2006. PubMed ID: 16982909. Show all entries for this paper.