Search CTL/CD8+ T-Cell Epitope Database

Found 86 matching records:

Displaying record number 58853

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Gag(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	QK10
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Country	Canada
Experimental methods	Flow cytometric T-cell cytokine assay, Intracellular cytokine staining, Tetramer binding
Keywords	characterizing CD8+ T cells

Notes

Gene array studies were conducted in 35 subjects, comparing their immune expression in CTLs from acute/early infection to chronically-infected CTL. It was found that profound metabolic, proliferative and apoptotic-susceptibility differences existed. Acute/early CTL secreted less γ-IFN, but were more cytotoxic. IL-7R expression and ability to secrete IL-2 were correlated with viral set point. Stress and hyperproliferation negatively affect the transition from early/acute to chronic functional CTLs.
HLA-A*0301-QVPLRPMTYK tetramers were used to determine CTLs and their ability to secrete cytokines upon stimulation with QK10.

References

Trautmann2012 Lydie Trautmann, Florentin-Martial Mbitikon-Kobo, Jean-Philippe Goulet, Yoav Peretz, Yu Shi, Julien Van Grevenynghe, Francesco Andrea Procopio, Mohamad Rachid Boulassel, Jean-Pierre Routy, Nicolas Chomont, Elias K. Haddad, and Rafick-Pierre Sekaly. Profound Metabolic, Functional, and Cytolytic Differences Characterize HIV-Specific CD8 T Cells in Primary and Chronic HIV Infection. Blood, 120(17):3466-3477, 25 Oct 2012. PubMed ID: 22955926. Show all entries for this paper.

Displaying record number 57516

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	QK10
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.

Displaying record number 53098

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(71-80)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Species (MHC/HLA)	human(A*03)
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 T-helper cell responses. Only patients starting with moderately high viral load (VL) were able to reduce the VL set point. HIV-1 specific CD8+ T-cell responses were shown to increase significantly until the end of the follow up.
9/14 patients recognized this epitope, it was the most recognized of six A*03 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 56756

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location
Epitope	`QVPLRPMTYK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*03)
Immunogen	HIV-1 infection
Patient MHC/HLA	MM39: A02:01, A03:01, B15:01, B35:01, C03:03:01, C04:01:01:01; MM12: A03, A68, B07, B44, C07, C07
Country	United Kingdom
Experimental methods	CD8 T-cell Elispot - IFNγ, Tetramer binding
Keywords	acute/early infection, optimal epitope

Notes

The study analyzed the kinetics of the HIV-specific CD8+ T-cell response in 21 acutely infected subjects. The first responses peaked at as early as 5 days, but were of limited epitope breadth. Responses of additional specificities expanded in subsequent waves, resulting in successive shifts in epitope immunodominance over time. The results document the preferential expansion of CD8+ T cells recognizing a subset of epitopes in acute infection and suggest that the initial T-cell response may influence the efficiency of viral containment in early infection.
QVPLRPMTYK is an optimally-defined epitope targeted by the first-analyzed T-cell responses in acute infection in patient MM12.
As indicated in parentheses, other patients had T-cell responses to peptides or epitopes containing all or most of QVPLRPMTYK: QEEEEVGFPVRPQVPLRPMT (MM23 & MM46), EVGFPVRPQVPLRPMTYK (MM33 & MM39), RPQVPLRPMTYKAAVDLSHF (MM25, MM28 & MM55), and VPLRPMTY (MM28). Dynamics of these responses & peptide sequences are shown in Fig. S2-S3 of Yang2019 which developed mathematical models with the Turnbull2009 dataset.

References

Turnbull2009 Emma L. Turnbull, MaiLee Wong, Shuyi Wang, Xiping Wei, Nicola A. Jones, Karen E. Conrod, Diana Aldam, Jo Turner, Pierre Pellegrino, Brandon F. Keele, Ian Williams, George M. Shaw, and Persephone Borrow. Kinetics of Expansion of Epitope-Specific T Cell Responses During primary HIV-1 Infection. J. Immunol., 182(11):7131-7145, 1 Jun 2009. PubMed ID: 19454710. Show all entries for this paper.

Yang2019 Yiding Yang, and Vitaly V. Ganusov. Defining Kinetic Properties of HIV-Specific CD8(+) T-Cell Responses in Acute Infection. Microorganisms, 7(3):microorganisms7030069 doi, Mar 2019. PubMed ID: 30836625 Show all entries for this paper.

Displaying record number 54753

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef
Epitope	`QVPLRPMTYK`	Epitope Alignment
Species (MHC/HLA)	human(A*03)
Immunogen	peptide-HLA interaction
Experimental methods	Tetramer binding
Keywords	binding affinity

Notes

MHC can exert a protective effect on HIV-1 disease progression by the interaction of MHC Class I molecules with Killer Inhibitory Receptors (KIR) of the innate immune system. Here, KIR3DS1, a putative stimulatory receptor and allele of the inhibitory KIR3DL1, is studied. Bw4 MHC Class I proteins were implicated in this KIR's ligand specificity, but the authors were unable to generate binding of Bw4Ile80 tetramers in complex with epitopes to KIR3DS1 transiently expressed on 293-T cells, using a panel of HIV-epitopes differing at p7 and p8.
This epitope, QVPLRPMTYK (MHC Class I restriction, serotype Bw6) complexed with MHC A03 as a tetramer was unable to bind KIR3DS1 at 4, 20 and 37C.

References

Gillespie2007 Geraldine M. A. Gillespie, Arman Bashirova, Tao Dong, Daniel W. McVicar, Sarah L. Rowland-Jones, and Mary Carrington. Lack of KIR3DS1 Binding to MHC Class I Bw4 Tetramers in Complex with CD8+ T Cell Epitopes. AIDS Res. Hum. Retroviruses, 23(3):451-455, Mar 2007. PubMed ID: 17411378. Show all entries for this paper.

Displaying record number 57291

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	QK10
Subtype	B
Species (MHC/HLA)	human(A*03)
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 QK10-Nef, QVPLRPMTYK restricted by A*03, 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.

Displaying record number 60067

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	QK10
Species (MHC/HLA)	human(A*03)
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.
QVPLRPMTYK had a significantly positive association with HLA A*03; it was recognized by 39/63 A*03-positive subjects and 33/278 A*03-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 1990

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	Nef-QK10
Subtype	B
Species (MHC/HLA)	human(A*03)
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*03, 9/20 (45%) 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 58533

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A03, A11, A31, B27, B*35)
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*03/A*11/A*31/B*27/B*35-restricted Nef optimal epitope QVPLRPMTYK was tested in a dual color EliSpot and 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 1124

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Species (MHC/HLA)	human(A*03:01)
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 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, 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.

Displaying record number 978

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82 NL43)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Species (MHC/HLA)	human(A*03:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

81 Tyr is critical for binding to A3.1.
C. Brander notes that this is an A*0301 epitope in the 1999 database.

References

Koenig1990 S. Koenig, T. R. Fuerst, L. V. Wood, R. M. Woods, J. A. Suzich, G. M. Jones, V. F. de la Cruz, R. T. Davey, Jr., S. Venkatesan, B. Moss, W. E. Biddison, and A. S. Fauci. Mapping the Fine Specificity of a Cytotoxic T Cell Response to HIV-1 Nef Protein. J. Immunol., 145:127-135, 1990. A 10 residue peptide that triggers CTL in association with the HLA A3.1 molecule was studied. Human cell transfectants were used to map a critical residue in the HLA A3.1 molecule for recognition, amino acid 152, which is present on the alpha-2 helix in HLA-A3.1 and is modified in the HLA A3.2 A3 allele. PubMed ID: 1694201. Show all entries for this paper.

Displaying record number 60987

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*03:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	25122: A01:01, A03:01, B07:02, B37:01, C06:02, C07:02; 51314: A03:01, A11:01, B35:03, B53:01, C04:01, C04:01
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.
QVPLRPMTYK, restricted by A*0301 , 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 1125

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82 LAI)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*03:01)
Immunogen
Experimental methods
Keywords	optimal epitope, A-list

Notes

C. Brander notes this is an A*0301 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 52578

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*03:01)
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.

Displaying record number 57853

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Species (MHC/HLA)	human(A*03:01)
Immunogen	HIV-1 infection
Country	United Kingdom
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords	rate of progression, early treatment

Notes

103 epitope-specific CTL responses were compared between 19 long-term ART patients who began therapy at the time of seroconversion and 15 long-term non-progressors. ART initiated at the time of seroconversion was associated with immunological features resembling long-term non-progressors.
As a representative example, ICS responses to A*0301-restricted epitope QVPLRPMTYK were examined in a long-term non-progressor.

References

Cellerai2011 Cristina Cellerai, Alexandre Harari, Hans Stauss, Sabine Yerly, Anna-Maria Geretti, Anne Carroll, Thynn Yee, Jonathan Ainsworth, Ian Williams, John Sweeney, Andrew Freedman, Margaret Johnson, Giuseppe Pantaleo, and Sabine Kinloch-de Loes. Early and Prolonged Antiretroviral Therapy Is Associated with an HIV-1-Specific T-Cell Profile Comparable to That of Long-Term Non-Progressors. PLoS One, 6(4):e18164, 2011. PubMed ID: 21483676. Show all entries for this paper.

Displaying record number 61241

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(263-272)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	QK10
Species (MHC/HLA)	human(A*03:01)
Immunogen	HIV-1 infection
Experimental methods	Other
Keywords	review, immunodominance, TCR usage, variant cross-reactivity

Notes

Recent findings of the HIV-specific TCR repertoire are reviewed here. Epitope QK10, QVPLRPMTYK-CTL avidity correlates with ability of infected individuals to respond to antigen with sensitivity, polyfunctionality and viral suppression.

References

Lissina2016 Anna Lissina, Lisa A. Chakrabarti, Masafumi Takiguchi, and Victor Appay. TCR Clonotypes: Molecular Determinants of T-Cell Efficacy against HIV. Curr. Opin. Virol., 16:77-85, Feb 2016. PubMed ID: 26874617. Show all entries for this paper.

Displaying record number 1123

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Species (MHC/HLA)	human(A*03:01)
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.
1/11 of the A2+ individuals was A3, and responded to QVPLRPMTYK as well as two other A3.1 epitopes.

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.

Displaying record number 986

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82 LAI)
Epitope	`QVPLRPMTYK`	Epitope Alignment
		Show epitope variants
Subtype	B
Species (MHC/HLA)	human(A*03:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords	rate of progression, escape

Notes

Alanine substitutions L76A, R77A, M79A, T80A significantly decreased immunogenicity of peptide.
Nef CTL clones (4N225) were infused into an HIV-1 infected volunteer to evaluate effects of infusion on viral load/patient health.
Infusion led to outburst of escape variants which resulted in higher viral load/accelerated disease progression.

References

Koenig1995 S. Koenig, A. J. Conley, Y. A. Brewah, G. M. Jones, S. Leath, L. J. Boots, V. Davey V, G. Pantaleo, J. F. Demarest, and C. Carter. Transfer of HIV-1-Specific Cytotoxic T Lymphocytes to an AIDS Patient Leads to Selection for Mutant HIV Variants and Subsequent Disease Progression. Nat. Med., 1(4):330-336, 1995. PubMed ID: 7585062. Show all entries for this paper.

Displaying record number 58242

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
		Show epitope variants
Subtype	B
Species (MHC/HLA)	human(A*03:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	MM39: A02:01, A03:01, B15:01, B35:01, C03:03:01, C04:01:01:01
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords	dynamics, escape, acute/early infection, autologous responses, characterizing CD8+ T cells

Notes

Multifunctionality of CTL against transmitted or founder HIV-1 isolates during early or acute infection was examined for correlation with escape mutation selection. The earliest CTL responses were oligofunctional, and progressively became more multifunctional. A significant association was found between total CTL response and order of escape selection, and between epitope entropy with the rate of emergence of escape mutants.
18-mer EVGFPVRPQVPLRPMTYK (Nef 65-82) shows evidence of late escape or variation by 639 days from onset of symptoms (DFOSx). This epitope elicited CTL response in patient MM39.

References

Ferrari2011 Guido Ferrari, Bette Korber, Nilu Goonetilleke, Michael K. P. Liu, Emma L. Turnbull, Jesus F. Salazar-Gonzalez, Natalie Hawkins, Steve Self, Sydeaka Watson, Michael R. Betts, Cynthia Gay, Kara McGhee, Pierre Pellegrino, Ian Williams, Georgia D. Tomaras, Barton F. Haynes, Clive M. Gray, Persephone Borrow, Mario Roederer, Andrew J. McMichael, and Kent J. Weinhold. Relationship between Functional Profile of HIV-1 Specific CD8 T Cells and Epitope Variability with the Selection of Escape Mutants in Acute HIV-1 Infection. PLoS Pathog., 7(2):e1001273, 2011. PubMed ID: 21347345. Show all entries for this paper.

Displaying record number 59175

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	nef 020-028
Subtype	B
Species (MHC/HLA)	human(A*03:01)
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*0301-restricted peptide gag 073-082, QVPLRPMTYK, was recognized by 6/10 B*57⁺ subjects with a mean intensity ˜1000 Sfc/10⁶ PBMCs and <500 Sfc/10⁶ ml for 6/13 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.

Displaying record number 57096

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82 DU422)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*03:01)
Immunogen	in vitro stimulation or selection
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, Tetramer binding
Keywords	dendritic cells

Notes

Three types of myeloid dendritic cells - monocytic dendritic cells, Langerhans cells, and interstitial dermal-intestinal dendritic cells - were shown to be able to prime CD8+ T-cell responses to HIV-1. Primed monocytic dendritic cells from 2 uninfected adult donors had broad primary T-cell reactivity, reacting with 15mers containing 42 known epitopes in Gag, Env, and Nef.
One of the reactive 15mers contained optimal epitope QVPLRPMTYK, which was restricted by HLA A*0301.

References

Colleton2009 Bonnie A. Colleton, Xiao-Li Huang, Nada M. Melhem, Zheng Fan, Luann Borowski, Giovanna Rappocciolo, and Charles R. Rinaldo. Primary Human Immunodeficiency Virus Type 1-Specific CD8+ T-Cell Responses Induced by Myeloid Dendritic Cells. J. Virol., 83(12):6288-6299, Jun 2009. PubMed ID: 19357176. Show all entries for this paper.

Displaying record number 53827

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef
Epitope	`QVPLRPMTYK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*03:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	A01:01, A03:01, B08:01, B51:01
Country	United Kingdom
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding
Keywords	escape

Notes

CTL responses and escape were analyzed in 4 homosexual couples where blood samples were available within weeks of estimated transmission. When the recipient had the same HLA type as the donor, CTL escape variants prevented a CTL response to those epitopes in the recipient. Even when the HLA alleles were different in the transmitting couple, a single escape mutation in one epitope can abolish CTL recognition of an overlapping epitope of distinct restriction in the recipient. In an early acute infection of the donor, the precise timing of transmission determines the viral variants transmitted.
Two variants of this epitope, QVPvRPMTYK and QaPLRPMTYK, were found in 1 donor. The QaPLRPMTYK substitution reduced the binding affinity for A*0301 by 52%.

References

Milicic2005 Anita Milicic, Charles T. T. Edwards, Stéphane Hué, Julie Fox, Helen Brown, Tilly Pillay, Jan W. Drijfhout, Jonathan N. Weber, Edward C. Holmes, Sarah J. Fidler, Hua-Tang Zhang, and Rodney E. Phillips. Sexual Transmission of Single Human Immunodeficiency Virus Type 1 Virions Encoding Highly Polymorphic Multisite Cytotoxic T-Lymphocyte Escape Variants. J. Virol., 79(22):13953-13962, Nov 2005. PubMed ID: 16254331. Show all entries for this paper.

Displaying record number 57758

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef
Epitope	`QVPLRPMTYK`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(A*03:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	A03:01, A74:01, B49:01, B58:02, C06:02, C07:01
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 A*0301-positive acutely HIV-1-infected individual had a peptide response to presumed optimal epitope QVPLRPMTYK within peptide QVPLRPMTYKAAFDL. Autologous viral escape occurred at 11 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 55009

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
		Show epitope variants
Epitope Name	QVP
Species (MHC/HLA)	human(A*03:01)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, TCR usage, variant cross-reactivity, characterizing CD8+ T cells

Notes

Functional cross-reactivity of CD8 responses to HIV-1 epitopes restricted by different HLA-alleles was analyzed. It was shown that epitope-specific responses with the most efficient cross-recognition were strongly associated with delayed disease progression. Variant-cross recognition efficiency was linked to the dominant TCRs used for epitope recognition. Epitopes restricted by the same HLA-allele did not show similar variant cross-recognition efficiency, suggesting that the rate of disease progression might be associated with the quality of responses to certain critical epitopes.
This epitope, A3-QVP (that has no assoication with accelerated or delayed progression to AIDS) and its natural variants are less efficiently cross-recognized. Its alanine-substituted variants were inconsistent between individuals showing very efficient or poor cross-reactivity. CTLs responding to this epitope expressed the same predominant TCR Vbeta family, but individuals whose CTLs predominantly used TCR Vbeta 13.6 had poor cross-recognition of alanine substituted variants.

References

Turnbull2006 Emma L. Turnbull, A. Ross Lopes, Nicola A. Jones, David Cornforth, Phillipa Newton, Diana Aldam, Pierre Pellegrino, Jo Turner, Ian Williams, Craig M. Wilson, Paul A. Goepfert, Mala K. Maini, and Persephone Borrow. HIV-1 Epitope-Specific CD8+ T Cell Responses Strongly Associated with Delayed Disease Progression Cross-Recognize Epitope Variants Efficiently. J. Immunol., 176(10):6130-6146, 15 May 2006. PubMed ID: 16670322. Show all entries for this paper.

Displaying record number 59120

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
		Show epitope variants
Epitope Name	QK10
Subtype	B
Species (MHC/HLA)	human(A03:01, A11)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, CTL suppression of replication, Intracellular cytokine staining, Tetramer binding
Keywords	binding affinity, TCR usage

Notes

The impact of antigen sensitivity (AgS) and TCR avidity on HIV-suppressive capacity was interrogated using cell lines generated from CTL clones specific for 3 different conserved, immunodominant epitopes and isolated from HIV-1-infected patients. The study encompassed 3 different epitope sequence specificities (QK10 - QVPLRPMTYK, RY10 - RLRPGGKKKY, KK10- KRWIILGLNK), from 2 different HIV-1 proteins (Gag and Nef), 2 restricting HLA classes (HLA-A*0301 and HLA-B*27) and effects on 3 viral strains (LAI, JR-CSF, DH12). AgS (EC₅₀ in EliSpot) and TCR avidity (EC₅₀ of tetramer concentrations) were significantly correlated.
High TCR avidity CTL clones (A3-QK10/A3-RY10/B27-KK10) were found to more efficiently suppress HIV replication than lower TCR avidity clones, within each epitope specificity.
Differential HIV strain-dependent suppressive capacity was seen for various epitope-specific-CTL clones. This could be due to epitope sequence variations or changes in flanking sequence.
A3-QK10-specific clones effectively suppressed LAI strain HIV, but suppressed strains JR-CSF modestly and DH12 poorly. Though these clones displayed lower TCR avidity and AgS than A3-RY10 clones, they were more efficient at suppressing HIV replication. Flanking mutations are seen in strain DH12.

References

Lissina2014 Anna Lissina, Solène Fastenackels, Maria C. Inglesias, Kristin Ladell, James E. McLaren, Olivia Briceño, Emma Gostick, Laura Papagno, Brigitte Autran, Delphine Sauce, David A. Price, Asier Saez-Cirion, and Victor Appay. The Link between CD8+ T-Cell Antigen-Sensitivity and HIV-Suppressive Capacity Depends on HLA Restriction, Target Epitope and Viral Isolate. AIDS, 28(4):477-486, 20 Feb 2014. PubMed ID: 24384691. Show all entries for this paper.

Displaying record number 53016

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*03:01, A11)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, CD8 T-cell Elispot granzyme B
Keywords	Th1, characterizing CD8+ T cells

Notes

Only 20% of CD8+ T-cells produce IFN-gamma and granzyme B simultaneously (Tc1a). Two additional subpopulations of HIV specific CD8 cells are found, each one constituting 30-40% of the CD8 cell pool. One of these (Tc1b) secretes IFN-gamma only, and the other one (Tc1c) secretes GzB only.
None of three patients responded to this peptide with GzB producing cells, while all three responded with IFN-gamma producing cells.

References

Kleen2004 Thomas O. Kleen, Robert Asaad, Samuel J. Landry, Bernhard O. Boehm, and Magdalena Tary-Lehmann. Tc1 Effector Diversity Shows Dissociated Expression of Granzyme B and Interferon-gamma in HIV Infection. AIDS, 18(3):383-392, 20 Feb 2004. PubMed ID: 15090789. Show all entries for this paper.

Displaying record number 52434

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef
Epitope	`QVPLRPMTYK`	Epitope Alignment
Subtype	A, B, D
Species (MHC/HLA)	human, macaque(A*03:01, A11)
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 1507

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82 LAI)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	N1
Subtype	B
Species (MHC/HLA)	human(A03 supertype)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART, supertype

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 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.

Displaying record number 1744

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(71-80 93TH253 subtype CRF01)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Subtype	CRF01_AE
Species (MHC/HLA)	human(A*11)
Immunogen	HIV-1 infection
Experimental methods
Keywords	subtype comparisons

Notes

HLA-A*11 CRF01 (called subtype E in Bond et al.) epitopes were identified that stimulated CTL from HIV+ female sex workers (FSW) from Northern Thailand, of whom more than half were HLA-A*11 positive.
77 possible HLA-A*11 epitopes were first defined using EpiMatrix, these were screened for binding to A*11 finding and 26 bound, and 12 of these were epitopes for CTL responses from 8 HLA-A*11 positive FSWs, six were novel, six were previously identified.
This epitope was predicted by the EpiMatrix method to be likely to bind to A*11, and it served as an epitope in the FSWs, it was one of the six A*11 epitopes that had been previously defined.
4/8 tested FSWs recognized this epitope.
An HLA-A*11 tetramer was made for this epitope, which was recognized by two subjects -- only one subject had an expanded tetramer staining T-cell population after in vitro stimulation.
This epitope was highly conserved in other subtypes, and exact matches were common.

References

Bond2001 K. B. Bond, B. Sriwanthana, T. W. Hodge, A. S. De Groot, T. D. Mastro, N. L. Young, N. Promadej, J. D. Altman, K. Limpakarnjanarat, and J. M. McNicholl. An HLA-directed molecular and bioinformatics approach identifies new HLA-A11 HIV-1 subtype E cytotoxic T lymphocyte epitopes in HIV-1-infected Thais. AIDS Res. Hum. Retroviruses, 17(8):703-17, 20 May 2001. PubMed ID: 11429111. Show all entries for this paper.

Displaying record number 55240

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*11)
Immunogen	HIV-1 infection
Country	China
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Other
Keywords	immunodominance, assay or method development, optimal epitope

Notes

HLA-A11-restricted CTL epitopes in 2 male Han Chinese subjects (one ART naive and one receiving HAART) were determined. A novel epitope was discovered and 5 other putative epitopes confirmed using 425 overlapping peptides spanning the entire HIV-1 clade B proteome. By employing intracellular cytokine staining, the authors developed a new method of mapping optimal epitopes and defining their HLA restriction efficiently. In spite of its being the most common HLA type in China, A*11-restricted epitopes were recognized less frequently than other epitopes, and A*11-restricted responses formed a mean of only 13% of the responses against HIV.
This putative epitope, QVPLRPMTYK, was detected and confirmed within overlapping peptides EVGFPVRPQVPLRPMTYK and YKAAVDLSHFLKEKGGL. It was the immunodominant HLA-A*11 restricted epitope in 10 subjects tested.

References

Wang2007 Shaoyang Wang, Yongtao Sun, Song Zhai, Yan Zhuang, Shuguang Zhao, Whenzhen Kang, Xinhong Li, Dedong Huang, Xu G. Yu, Bruce D. Walker, and Marcus A. Altfeld. Identification of HLA-A11-Restricted HIV-1-Specific Cytotoxic T-Lymphocyte Epitopes in China. Curr. HIV Res., 5(1):119-128, Jan 2007. PubMed ID: 17266563. Show all entries for this paper.

Displaying record number 60068

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	QK10
Species (MHC/HLA)	human(A*11)
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.
QVPLRPMTYK had a significantly positive association with HLA A*11; it was recognized by 13/28 A*11-positive subjects and 20/250 A*11-negative subjects.

References

Displaying record number 974

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Species (MHC/HLA)	human(A11)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

Soluble factors in supernatant from both an HIV-specific cloned CTL line and an EBV (Epstein-Barr-virus) CTL line inhibit viral replication, but do not block viral entry in CD4+ T lymphocytes, by a noncytotoxic mechanism.

References

LeBorgne2000 S. Le Borgne, M. Fevrier, C. Callebaut, S. P. Lee, and Y. Riviere. CD8(+)-Cell antiviral factor activity is not restricted to human immunodeficiency virus (HIV)-specific T cells and can block HIV replication after initiation of reverse transcription. J. Virol., 74:4456-64, 2000. PubMed ID: 10775581. Show all entries for this paper.

Displaying record number 1372

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	QVP
Species (MHC/HLA)	human(A11)
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-A11 study subjects recognized this CTL epitope.
Patient SC18(HLA A2/11, B8/44, Cw06/0701, DR3/7, DR52/53, DQ2) recognizes the epitopes ACQGVGGPGHK, QVPLRPMTYK, AVDLSHFLK, and one called QIY but not fully described -- he had brief therapy upon seroconversion and has had low viral load during 600 days of follow up.

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.

Displaying record number 1656

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Species (MHC/HLA)	human(A11)
Immunogen	HIV-1 exposed seronegative, HIV-1 infection
Experimental methods
Keywords	HIV exposed persistently seronegative (HEPS)

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.

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 1702

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Species (MHC/HLA)	human(A11)
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 1724

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(71-80 93TH253 subtype CRF01)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	N73-82
Subtype	CRF01_AE
Species (MHC/HLA)	human(A11)
Immunogen	HIV-1 exposed seronegative, HIV-1 infection
Experimental methods
Keywords	HIV exposed persistently seronegative (HEPS)

Notes

This was a study of HIV-1 exposed persistently seronegative (HEPS) female sex workers in Chiang Mai, northern Thailand.
HLA-A11 is very common in this population, and was enriched among the HEPS sexworkers -- weak CTL responses were detected in 4/7 HEPS women, and CTL responses were found in 8/8 HIV+ controls, and 0/9 HIV- women that were not exposed.
This epitope was weakly reactive in HEPS study subjects 265 who was HLA A2/A11 and 128 who was HLA A11/A33, and after a second in vitro stimulation, in study subject 256 who was HLA A11/33, making it the most reactive epitope tested in HLA-A11 HEPS women, with 3/4 responding.
This epitope was strongly reactive in HIV+ study subject 053 who carried HLA-A11.

References

Sriwanthana2001 B. Sriwanthana, T. Hodge, T. D. Mastro, C. S. Dezzutti, K. Bond, H. A. Stephens, L. G. Kostrikis, K. Limpakarnjanarat, N. L. Young, S. H. Qari, R. B. Lal, D. Chandanayingyong, and J. M. McNicholl. HIV-specific cytotoxic T lymphocytes, HLA-A11, and chemokine-related factors may act synergistically to determine HIV resistance in CCR5 delta32-negative female sex workers in Chiang Rai, northern Thailand. AIDS Res. Hum. Retroviruses, 17(8):719-34, 20 May 2001. PubMed ID: 11429112. Show all entries for this paper.

Displaying record number 980

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82 LAI)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A11)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

Development of a retroviral vector (pNeoNef) to generate autologous CTL targets.
Hunziker et al., Aids Res. Hum. Retro. 14(11):921-4 (1998) suggests that HLA-A2 does not in fact present this epitope.
The initial assignment of HLA-A2 presentation for this epitope was based on a serological HLA typing. Subsequently, the authors revisited the issue with genetic HLA typing and found that HLA-A11 was the correct presenting molecule (Dr. Florence Buseyne, pers. comm., 2000)

References

Robertson1993 M. N. Robertson, F. Buseyne, O. Schwartz, and Y. Riviere. Efficient Antigen Presentation to Cytotoxic T Lymphocytes by Cells Transduced with a Retroviral Vector Expressing the HIV-1 Nef Protein. AIDS Res. Hum. Retroviruses, 9:1217-1223, 1993. This paper presents a retroviral vector system for antigen presentation to CTLs. As part of the controls to test their system, they study the response to specific Nef peptides, which contain the dominant CTL epitopes in Nef in their study subject. PubMed ID: 7511396. Show all entries for this paper.

Displaying record number 52318

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	QVP
Species (MHC/HLA)	human(A11)
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.

Displaying record number 52358

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef
Epitope	`QVPLRPMTYK`	Epitope Alignment
Species (MHC/HLA)	human(A11)
Immunogen	HIV-1 infection
Patient MHC/HLA	A11, A2, B60, B8, 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 -- two patients recognized this epitope, one using HLA-A3, one using HLA-A11.
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 981

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82 LAI)
Epitope	`QVPLRPMTYK`	Epitope Alignment
		Show epitope variants
Subtype	B
Species (MHC/HLA)	human(A11)
Immunogen	HIV-1 infection
Experimental methods
Keywords	review, escape

Notes

Mutational variation in HIV epitopes in individuals with appropriate HLA types can result in evasion of CTL response.
QVPLRPMTsr substitutions resulted to a very low binding to HLA-A11.
The epitope QVPLRPMTYK was entirely conserved in 9 isolates from the donor who did not recognize this epitope, whereas there were flanking mutations T71R and A83G, suggesting processing escape.
Goulder1997e is a review of immune escape that summarizes this study.

References

Couillin1994 I. Couillin, B. Culmann-Penciolelli, E. Gomard, J. Choppin, J. P Levy, J. G. Guillet, and S. Sarasgosti. Impaired Cytotoxic T Lymphocyte Recognition Due to Genetic Variations in the Main Immunogenic Region of the Human Immunodeficiency Virus 1 NEF Protein. J. Exp. Med., 180:1129-11234, 1994. HIV-1 HLA-A11 and -B18 restricted epitopes were sequenced from donors who do and do not express the HLA-A11 and B18 molecule. Selective variations were only detected in virus isolated from individuals expressing the appropriate HLA type. Variant peptides with single substitutions within the minimal epitope did not always completely abrogate HLA binding, suggesting that multiple alterations within a particular epitope may need to accumulate during disease progression to allow viral escape. PubMed ID: 7520468. 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.

Displaying record number 982

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82 LAI)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A11)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

Mutations found in this epitope in HLA-A11 positive and negative donors were characterized.

References

Couillin1995 I. Couillin, F. Connan, B. Culmann-Penciolelli, E. Gomard, J.-G. Guillet, and J. Choppin. HLA-Dependent Variations in Human Immunodeficiency Virus Nef Protein Alter Peptide/HLA binding. Eur. J. Immunol., 25:728-732, 1995. Viral sequences across this region were compared from 3 HLA-A11 positive and 10 negative donors. Substitutions that were found only in the 3 HLA-A11 donors did not promote HLA-A11 assembly. Substitutions that were found in both HLA-A11 positive and negative donors, however, did not markedly alter the reactivity of the peptides. This suggests that substitutions that result in loss of HLA-A11 occur mainly in HLA-A11 positive donors. PubMed ID: 7705402. Show all entries for this paper.

Displaying record number 53484

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	QK10
Subtype	B
Species (MHC/HLA)	human(A11)
Immunogen	HIV-1 infection
Patient MHC/HLA	A11, A2, B18, B44, C*12, Cw5
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords

Notes

4/14 optimal HIV-1 T-cell epitopes in a subject underwent mutation associated with dramatic loss of the original CD8 response. For 1 of the escape variants, a novel CD8 T-cell response equal in magnitude to the wildtype, was generated. CD8 T-cell recognizing the variant epitope utilized a distinct T-cell receptor and did not exhibit any cross-reactivity against the wildtype.
This epitope did not vary.

References

Allen2005 Todd M. Allen, Xu G. Yu, Elizabeth T. Kalife, Laura L. Reyor, Mathias Lichterfeld, Mina John, Michael Cheng, Rachel L. Allgaier, Stanley Mui, Nicole Frahm, Galit Alter, Nancy V. Brown, Mary N. Johnston, Eric S. Rosenberg, Simon A. Mallal, Christian Brander, Bruce D. Walker, and Marcus Altfeld. De Novo Generation of Escape Variant-Specific CD8+ T-Cell Responses Following Cytotoxic T-Lymphocyte Escape in Chronic Human Immunodeficiency Virus Type 1 Infection. J. Virol., 79(20):12952-12960, Oct 2005. PubMed ID: 16188997. Show all entries for this paper.

Displaying record number 53564

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A11)
Immunogen	HIV-1 infection
Patient MHC/HLA	A11, A2, B18, B44, C*12, Cw5
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords

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.
This epitope was reactive, but escape mutations did not accrue in it over time.

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.

Displaying record number 53780

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	QK9
Species (MHC/HLA)	(A11)
Immunogen
Experimental methods
Keywords	review, immunodominance, escape, acute/early infection, early-expressed proteins, kinetics, viral fitness and reversion

Notes

This review discusses the importance of 3 factors that impact the selection of immunodominant epitopes in acute HIV infection: i) the kinetics of viral protein expression, ii) the HLA class I background of the infected individual, and iii) the autologous sequence of the infecting virus. This is 1 of 12 peptides listed as immunodominant in acute HIV-1 infection.

References

Lichterfeld2005 Mathias Lichterfeld, Xu G. Yu, Sylvie Le Gall, and Marcus Altfeld. Immunodominance of HIV-1-Specific CD8+ T-Cell Responses in Acute HIV-1 Infection: At the Crossroads of Viral and Host Genetics. Trends Immunol., 26(3):166-171, Mar 2005. PubMed ID: 15745859. Show all entries for this paper.

Displaying record number 54255

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	A11-QK10(Nef)
Species (MHC/HLA)	human(A11)
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.

Displaying record number 54504

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(74-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Species (MHC/HLA)	human(A11)
Immunogen	HIV-1 infection
Patient MHC/HLA	A11, A24, B44, B55
Country	United Kingdom
Experimental methods	Flow cytometric T-cell cytokine assay, Other
Keywords	HAART, ART, immunodominance, TCR usage, memory cells

Notes

The effect of HAART on the population size, phenotype and function of HIV- and HCMV-specific CTL clones was analyzed. It was determined that the clonal composition of gag and env HIV-specific CD8 T-cells did not change after HAART. Following HAART, the size of immunodominant HIV-specific CD8 T-cell clones was found to diminish even with the relative preservation of functional memory responses. Maintainance of such strong functional responses implied the preferential loss of HIV-specific cells that have reduced cloning efficiency in vitro. HCMV-specific CTL clones had different kinetics and phenotypes than HIV-specific CTL clones in the same subject.

References

Weekes2006 Michael P. Weekes, Mark R. Wills, J. G. Patrick Sissons, and Andrew J. Carmichael. Large HIV-Specific CD8 Cytotoxic T-Lymphocyte (CTL) Clones Reduce Their Overall Size But Maintain High Frequencies of Memory CTL Following Highly Active Antiretroviral Therapy. Immunology, 118(1):25-38, May 2006. PubMed ID: 16630020. Show all entries for this paper.

Displaying record number 1415

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-81)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Species (MHC/HLA)	human(A11, A2, A3, B35)
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.

Displaying record number 55190

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location
Epitope	`QVPLRPMTYK`	Epitope Alignment
Species (MHC/HLA)	human(A11, A3)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	supertype, HLA cross-presentation

Notes

100 HIV-infected subjects were tested for response to optimally-defined CTL epitopes regardless of the subject's HLA type. Half of all detected responses were seen in the absence of the originally reported restricting HLA class I allele, and only 3% of epitopes were recognized exclusively in the presence of their original allele. Statistical and experimental methods were used to define additional HLA alleles associated with the epitopes.
Based on a prediction of the minimum number of HLA alleles needed to cover the HLA representation in all responders to this epitope, a minimum set of 6 alleles was found: 2 alleles previously known to be associated (A03, A11) and 4 additional alleles (A02, A33, B44, Cw07).
In addition to its known HLA associations (A03, A11), an additional HLA (A34) was statistically predicted to be associated with this epitope.

References

Frahm2007b Nicole Frahm, Karina Yusim, Todd J. Suscovich, Sharon Adams, John Sidney, Peter Hraber, Hannah S. Hewitt, Caitlyn H. Linde, Daniel G. Kavanagh, Tonia Woodberry, Leah M. Henry, Kellie Faircloth, Jennifer Listgarten, Carl Kadie, Nebojsa Jojic, Kaori Sango, Nancy V. Brown, Eunice Pae, M. Tauheed Zaman, Florian Bihl, Ashok Khatri, Mina John, Simon Mallal, Francesco M. Marincola, Bruce D . Walker, Alessandro Sette, David Heckerman, Bette T. Korber, and Christian Brander. Extensive HLA Class I Allele Promiscuity among Viral CTL Epitopes. Eur. J. Immunol., 37(9):2419-2433, Sep 2007. PubMed ID: 17705138. Show all entries for this paper.

Displaying record number 55914

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	QK10(Nef)
Subtype	B
Species (MHC/HLA)	human(A11, A3)
Immunogen	HIV-1 infection
Country	China
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	variant cross-reactivity, 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.
HLA-A3- and -A11-restricted epitope QVPLRPMTYK elicited an immune response in Chinese HIV-1 positive subjects as part of peptides EVGFPVRPQVPLRPMTYK and QVPLRPMTYKGALDLSHF.
1 of the 3 HLA-A3 carriers responded to a QVPLRPMTYK-containing peptide with average magnitude of CTL response of 230 SFC/million PBMC (author communication and Fig.1). 13 of the 28 HLA-A11 carriers responded to QVPLRPMTYK-containing peptide EVGFPVRPQVPLRPMTYK with average magnitude of CTL response of 263 SFC/million PBMC; and 5 of the 28 HLA-A11 carriers responded to QVPLRPMTYK-containing peptide QVPLRPMTYKGALDLSHF with average magnitude of CTL response of 133 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.

Displaying record number 57830

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	QK10
Subtype	B
Species (MHC/HLA)	human(A11, A3)
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.
QVPLRPMTYK 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.

Displaying record number 53728

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82 BRU)
Epitope	`QVPLRPMTYK`	Epitope Alignment
		Show epitope variants
Subtype	B, CRF02_AG
Species (MHC/HLA)	human(A11, A3)
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 0/9 CRF02_AG-infected Ivorians, and 2/9 B-infected French subjects.
3/8 Ivorians carried a substitution in this epitope, while only 1/5 B clade infected French people did, QVPvRPMTYK, and the substitution was found in one of the people that recognized the peptide.

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.

Displaying record number 54958

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Species (MHC/HLA)	(A11, A3, A30)
Immunogen	peptide-HLA interaction
Experimental methods	HLA binding
Keywords	binding affinity, immunodominance

Notes

Interaction between purified HLA-A3 molecules and several dominant CD8 epitopes was characterized. Amplitude, stability, and kinetic parameters of the interaction between HLA-A3, peptides, and anti-HLA mAbs were tested.
Epitopes tested bound strongly to HLA-A3 and formed very stable complexes.
Gag epitope RLRPGGKKK and Nef epitope RLAFHHVAR complexes with HLA-A3 were not recognized by the A11.1 MAb specific to HLA-A3 alleles. The proposed explanation was that Arg at position P1 of the peptide may push the α2 helix residue and affect MAb recognition.

References

Racape2006a Judith Racape, Francine Connan, Johan Hoebeke, Jeannine Choppin, and Jean-Gérard Guillet. Influence of Dominant HIV-1 Epitopes on HLA-A3/Peptide Complex Formation. Proc. Natl. Acad. Sci. U.S.A., 103(48):18208-18213, 28 Nov 2006. PubMed ID: 17116886. Show all entries for this paper.

Displaying record number 979

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82 BRU)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Species (MHC/HLA)	human(A11, A3, B35)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

Nef CTL clones from HIV+ donors.

References

Culmann1991 B. Culmann, E. Gomard, M.-P. Kieny, B. Guy, F. Dreyfus, A.-D. Saimot, D. Sereni, D. Sicard, and J.-P. Levy. Six Epitopes with Human Cytotoxic CD8+ Cells in the Central Region of the HIV-1 Nef Protein. J. Immunol., 146:1560-1565, 1991. Nef-specific CTL were generated from six seropositive donors. Six epitopes were defined, all localized to two regions in the central part of Nef. Some epitopes could be recognized in the contexts of several HLA class I molecules. Peptides were based on BRU epitopes: QVPLRPMTYK, HLA A3, A11, B35; AAVDLSHFLKEK, HLA A11; HTQGYFPQWQ, HLA B17;TQGYFPQWQNYT, HLA B17, B37, NYTPGPGVRYPLT, HLA B7; and GVRYPLTFGWCYKLVP, HLA B18). PubMed ID: 1704397. Show all entries for this paper.

Displaying record number 57817

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef
Epitope	`QVPLRPMTYK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*11:01)
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 QVPLRPMTYK was recognized by 5/6 A*1101-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 59488

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef( pNL4-3)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	QK10
Subtype	B
Species (MHC/HLA)	human(A*11:01)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, TCR binding
Keywords	assay or method development, novel epitope

Notes

Deep Ligand Sequencing (DLS) was used to identify 37 novel HLA-A*1101-restricted epitopes, and 5 previously published ones. HLA-A*1101-expressing CD4⁺ T cells were infected with HIV strain pNL4-3; soluble HLA-A*1101-ligand was recovered and purified, and then ligands (i.e. epitopes) were acid-released. A combination of chromatography and mass spectrometry used to separate the distinct peptides. For each epitope, the HLA binding affinity and median EliSpot response in 23 A*1101-positive patients were determined. This is the first report of direct elution of HIV-1 genome-encoded epitopes.
Gag and N-terminal Nef epitopes dominate the antigenic profile of epitopes over other HIV-1 proteins (Pol, Env, Vpu). Nef and Pol epitopes, however, were widely recognized. Immunologically reactive epitopes are often atypical in length, particularly in epitope hotspots of Gag and Nef. Epitopes discovered were primarily a result of de novo protein synthesis in the host cell instead of secretory pathway peptide processing.
QVPLRPMTYK, QK10, had high TCR binding and was recognized by 19/23 A*1101-positive patients with a median magnitude of 630 SFU/10⁶ PBMC. Nef-QK10 was one of the most reactive peptides evaluated, both in strength and frequency of response.

References

Yaciuk2014 Jane C. Yaciuk, Matthew Skaley, Wilfried Bardet, Fredda Schafer, Danijela Mojsilovic, Steven Cate, Christopher J. Stewart, Curtis McMurtrey, Kenneth W. Jackson, Rico Buchli, Alex Olvera, Samandhy Cedeño, Montserrat Plana, Beatriz Mothe, Christian Brander, John T. West, and William H. Hildebrand. Direct Interrogation of Viral Peptides Presented by the Class I HLA of HIV-Infected T Cells. J. Virol., 88(22):12992-13004, Nov 2014. PubMed ID: 25165114. Show all entries for this paper.

Displaying record number 57646

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	Nef73
Subtype	B
Species (MHC/HLA)	human(A*11:01)
Immunogen	HIV-1 infection
Country	Japan
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding, Intracellular cytokine staining, Relative replication capacity assay, Tetramer binding
Keywords	rate of progression, immunodominance

Notes

No correlation was found between ability of A*1101-restricted CTLs recognizing immunodominant epitopes to suppress replication in vitro and the appearance of escape mutants. Results suggest that escape mutations are selected by HIV-1-specific CTLs that have a stronger ability to recognize HIV-1 in vivo but not in vitro.
13/16 A*1101-positive individuals had CD8+ T cells specific for this epitope.
Analysis using 7 Nef73-specific CTL clones confirmed the strong ability of the Nef73-specific CTL clones to suppress HIV-1 replication.
Nef73-specific ones did not select any escape mutant. The 9F mutation was frequently found, but there was no significant difference in the frequency of this mutation between the HLA-A*1101-positive and -negative subjects.

References

Koizumi2010 Hirokazu Koizumi, Masao Hashimoto, Mamoru Fujiwara, Hayato Murakoshi, Takayuki Chikata, Mohamed Ali Borghan, Atsuko Hachiya, Yuka Kawashima, Hiroshi Takata, Takamasa Ueno, Shinichi Oka, and Masafumi Takiguchi. Different In Vivo Effects of HIV-1 Immunodominant Epitope-Specific Cytotoxic T Lymphocytes on Selection of Escape Mutant Viruses. J. Virol., 84(11):5508-5519, Jun 2010. PubMed ID: 20335254. Show all entries for this paper.

Displaying record number 53049

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Subtype	B, CRF01_AE
Species (MHC/HLA)	(A*11:01)
Immunogen
Country	Thailand
Experimental methods
Keywords	HIV exposed persistently seronegative (HEPS), immunodominance, structure

Notes

HLA-A*1101 has been associated with resistance to acquisition of HIV-1 infection in female sex-workers in Thailand. Its crystal structure has been determined in association with two immunodominant A*1101 HIV-1 CTL epitopes. Its anchor residues are confirmed as P2(Ile/Val) and C-term (Lys). The backbone conformation of the peptides is defined as two bulges separated by a secondary anchor residue (P6 Ser or Met) that may offer various advantages in the selection and presentation of CTL epitopes by HLA-A*1101.

References

Li2004 Lenong Li and Marlene Bouvier. Structures of HLA-A*1101 Complexed with Immunodominant Nonamer and Decamer HIV-1 Epitopes Clearly Reveal the Presence of a Middle, Secondary Anchor Residue. J. Immunol., 172(10):6175-6184, 15 May 2004. PubMed ID: 15128805. Show all entries for this paper.

Displaying record number 54300

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	QK10
Subtype	B
Species (MHC/HLA)	human(A*11:01)
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.

Displaying record number 1205

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	( LAI)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*11:01)
Immunogen
Experimental methods
Keywords	optimal epitope, A-list

References

BuseynePerCom1999 F. Buseyne. Personal communication, 1999. Show all entries for this paper.

Displaying record number 984

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Species (MHC/HLA)	human(A3)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

Eighty two HIV-1-specific CTL clones from 5 long-term non-progressors were isolated and analyzed for breadth of response.
A sustained Gag, Env and Nef response was observed, and clones were restricted by multiple HLA epitopes, indicating a polyclonal response.
An A3+ subject had a strong response to this epitope, with 10/11 CTL clones being specific for this epitope, isolated at two time points, 1 year apart.

References

Lubaki1997 N. M. Lubaki, S. C. Ray, B. Dhruva, T. C. Quinn, R. F. Siliciano, and R. C. Bollinger. Characterization of a Polyclonal Cytolytic T Lymphocyte Response to Human Immunodeficiency Virus in Persons without Clinical Progression. J. Infect. Dis., 6:1360-1367, 1997. Five individuals were studied who survived HIV infection in good health for over 5 years. A broad polyclonal response was found to multiple proteins. PubMed ID: 9180175. Show all entries for this paper.

Displaying record number 975

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82 LAI)
Epitope	`QVPLRPMTYK`	Epitope Alignment
		Show epitope variants
Subtype	B
Species (MHC/HLA)	human(A3)
Immunogen	HIV-1 infection
Experimental methods
Keywords	epitope processing, escape

Notes

Mutations in Nef that flank this epitope, Thr71Lys and Ala83Gly, may account for an observed loss of CTL reactivity, with escape due to the introduction of proteasome processing defects.

References

Chassin1999 D. Chassin, M. Andrieu, W. Cohen, B. Culmann-Penciolelli, M. Ostankovitch, D. Hanau, and J. G. Guillet. Dendritic Cells Transfected with the nef Genes of HIV-1 Primary Isolates Specifically Activate Cytotoxic T Lymphocytes from Seropositive Subjects. Eur. J. Immunol., 29:196-202, 1999. PubMed ID: 9933101. Show all entries for this paper.

Displaying record number 977

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Species (MHC/HLA)	human(A3)
Immunogen	HIV-1 infection
Experimental methods
Keywords	subtype comparisons

Notes

Cross-clade CTL response was studied by determining the CTL activity in seven patients from Bangui, (6 A subtype, and 1 AG recombinant infections) and one A subtype infection from a person living in France originally from Togo, to different antigens expressed in vaccinia.
Pol reactivity: 8/8 had CTL to A subtype, and 7/8 to B subtype, and HIV-2 Pol was not tested.
Gag reactivity: 7/8 reacted with A or B subtype gag, 3/8 with HIV-2 Gag.
Nef reactivity: 7/8 reacted with A subtype, and 5/8 with B subtype, none with HIV-2 Nef.
Env reactivity: 3/8 reacted with A subtype, 1/8 with B subtype, none with HIV-2 Env.
One of the patients was shown to react to this epitope: QVPLRPMTYK.

References

Durali1998 D. Durali, J. Morvan, F. Letourneur, D. Schmitt, N. Guegan, M. Dalod, S. Saragosti, D. Sicard, J. P. Levy, and E. Gomard. Cross-Reactions between the Cytotoxic T-Lymphocyte Responses of Human Immunodeficiency Virus-Infected African and European Patients. J. Virol., 72:3547-3553, 1998. PubMed ID: 9557634. Show all entries for this paper.

Displaying record number 983

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82 LAI)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A3)
Immunogen	HIV-1 infection
Patient MHC/HLA	003: A02, A03, B07, B51; 023: A02, A03, B07, B51
Experimental methods
Keywords	review, escape

Notes

HLA-identical siblings, twin hemophiliac brothers, were both infected with the same batch of factor VIII.
Both had a response to this epitope.
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.

Displaying record number 1471

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	N1
Species (MHC/HLA)	human(A3)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART, escape

Notes

The epitope was recognized by patients 252#0 and 252#4 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.

Displaying record number 1847

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef( SF2)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Species (MHC/HLA)	human(A3)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

This epitope was mapped by ELISPOT in a study identifying new HLA-B60 epitopes, and was one of the epitopes presented by another HLA molecule in an HLA-B60 individual.

References

Altfeld2000 M. A. Altfeld, A. Trocha, R. L. Eldridge, E. S. Rosenberg, M. N. Phillips, M. M. Addo, R. P. Sekaly, S. A. Kalams, S. A. Burchett, K. McIntosh, B. D. Walker, and P. J. Goulder. Identification of dominant optimal HLA-B60- and HLA-B61-restricted cytotoxic T-lymphocyte (CTL) epitopes: rapid characterization of CTL responses by enzyme-linked immunospot assay. J. Virol., 74:8541, 2000. PubMed ID: 10954555. Show all entries for this paper.

Displaying record number 52150

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	A3-QK10
Subtype	B
Species (MHC/HLA)	human(A3)
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.
3/14 HLA-A3 positive individuals had detectable A3-restricted responses to this epitope during acute infection, but only 5/15 of HLA-A3 epitopes tested were targeted during acute infection. 5/7 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 52359

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef
Epitope	`QVPLRPMTYK`	Epitope Alignment
Species (MHC/HLA)	human(A3)
Immunogen	HIV-1 infection
Patient MHC/HLA	A3, B44, B64, Bw4, 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 -- two patients recognized this epitope, one using HLA-A3, one using HLA-A11.
The HIV-specific CD8+ T-cells had an intermediate maturation phenotype characterized by low levels of perforin and high levels of CD27 expression.

References

Displaying record number 52624

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A3)
Immunogen	HIV-1 infection
Patient MHC/HLA	A1, A3, B14, B7, C07:02, C08:02
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	binding affinity, acute/early infection, early-expressed proteins

Notes

All proteins were scanned and optimal epitopes were mapped in a study of CD8+ IFNγ T-cell responses in 21 men within 15-92 days post-HIV-1 infection. Subjects initially showed a narrow immune response with a mean of 2.3 epitopes recognized per patient. The immune response broadened later in infection. No correlation between the plasma viral load and the number of recognized epitopes or the frequency of IFNγ-secreting cells was observed, and there was no correlation between the functional avidity of a response and the abundance of IFNγ-secreting cells that recognized the epitope. The first epitopes to be recognized did not tend to be the most avid, and earliest responses tended to be directed against Nef, Tat, Vpr, and Env.
All HIV-1 proteins except Vpu were recognized, and responses to a total of 41 optimal epitopes were characterized; 24 had been identified previously. 48% of the total T-cell responses were directed against Nef and 43% were directed against Gag.
More common HLA alleles were less frequently used in primary infection than less common alleles, for example A3, B35, B57, and B62 were more frequently utilized than A1, A2, A30, and A44.

References

Cao2003 Jianhong Cao, John McNevin, Sarah Holte, Lisa Fink, Lawrence Corey, and M. Juliana McElrath. Comprehensive Analysis of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Gamma Interferon-Secreting CD8+ T Cells in Primary HIV-1 Infection. J. Virol., 77(12):6867-6878, Jun 2003. PubMed ID: 12768006. Show all entries for this paper.

Displaying record number 52978

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Species (MHC/HLA)	human(A3)
Immunogen	HIV-1 infection
Patient MHC/HLA	A3, A32, B15, B51, C*03, Cw6, DQ7, DR4, DR8
Country	Netherlands
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, escape

Notes

Both stable potential epitopes and epitopes with escape mutations were found in a patient with increasing viral load over a time period of 4 years. Fixation of escape mutations occurred sequentially and correlated with the rise in viral load and with the increased number of productively infected cells.
This is one of 17 potential epitopes from this individual, defined based on previously identified epitopes presented by appropriate HLA molecules. Full length genome sequence did not reveal changes in time in any of these epitopes over a four year period. Peptide pools initially revealed very little response to these epitopes, but this increased over time.

References

Geels2003 Mark J. Geels, Marion Cornelissen, Hanneke Schuitemaker, Kiersten Anderson, David Kwa, Jolanda Maas, John T. Dekker, Elly Baan, Fokla Zorgdrager, Remco van den Burg, Martijn van Beelen, Vladimir V. Lukashov, Tong-Ming Fu, William A. Paxton, Lia van der Hoek, Sheri A. Dubey, John W. Shiver, and Jaap Goudsmit. Identification of Sequential Viral Escape Mutants Associated with Altered T-Cell Responses in a Human Immunodeficiency Virus Type 1-Infected Individual. J. Virol., 77(23):12430-12440, Dec 2003. PubMed ID: 14610167. Show all entries for this paper.

Displaying record number 53036

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef
Epitope	`QVPLRPMTYK`	Epitope Alignment
Species (MHC/HLA)	human(A3)
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.
3/5 HLA A3+ infection-resistant men, compared to 1/3 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 53378

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	( B consensus)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	QK10
Subtype	B
Species (MHC/HLA)	human(A3)
Immunogen	HIV-1 infection
Patient MHC/HLA	A3, B14, B60, Cw3, Cw7; A1, A3, B14, B8, Cw7, Cw8
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.
2/9 individuals recognized this epitope, presented by HLA-A3.

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 53632

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Species (MHC/HLA)	human(A3)
Immunogen	HIV-1 infection
Patient MHC/HLA	A2, A3, B44, B7
Country	United States
Experimental methods	Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords	HAART, ART, escape, variant cross-reactivity

Notes

Evidence of continued viral evolution during HAART therapy despite low viral load was found in 1/5 patients studied.
The epitope QVPLRPMTYK was invariant (18/18 sequences) prior to therapy in the patient that recognized it.

References

Casazza2005a Joseph P. Casazza, Michael R. Betts, Brenna J. Hill, Jason M. Brenchley, David A. Price, Daniel C. Douek, and Richard A. Koup. Immunologic Pressure within Class I-Restricted Cognate Human Immunodeficiency Virus Epitopes during Highly Active Antiretroviral Therapy. J. Virol., 79(6):3653-3663, Mar 2005. PubMed ID: 15731259. Show all entries for this paper.

Displaying record number 53828

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
		Show epitope variants
Subtype	C
Species (MHC/HLA)	human(A3)
Immunogen	HIV-1 infection
Patient MHC/HLA	A03:01, A74:01, B15:10, B35:01, C04:01; A03:01, A68, B07:02, B15:10, C04:01, C*07:02
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.
QVPLRPMTYK is the C subtype consensus form of an epitope recognized in a mother, who carried this autologous variant: QVPLRPMTfK. QVPLRPMTfK was the dominant form in her infant at 2 weeks of age, but new variants rapidly emerged: QVPLkPMTfK, QVPLRPMnYK, QVPvRPMTfK, QVPLRPMsYr, QVPLRPMsYK.

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 54240

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	A3-QK10(Nef)
Species (MHC/HLA)	human(A3)
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

Displaying record number 54876

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location
Epitope	`QVPLRPMTYK`	Epitope Alignment
Species (MHC/HLA)	human(A3)
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.

Displaying record number 60072

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	QK10
Species (MHC/HLA)	human(A*33)
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.
QVPLRPMTYK had a significantly positive association with HLA A*33; it was recognized by 2/15 A*33-positive subjects and 1/197 A*33-negative subjects.

References

Displaying record number 60071

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	QK10
Species (MHC/HLA)	human(A*34)
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.
QVPLRPMTYK had a significantly positive association with HLA A*34; it was recognized by 4/8 A*34-positive subjects and 6/217 A*34-negative subjects.

References

Displaying record number 1619

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(94-103)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Species (MHC/HLA)	human(A3 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 3/5 HLA-A3 supertype alleles (A*0301, A*1101, A*3101, A*3301 and A*6801).

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.

Displaying record number 60070

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	QK10
Species (MHC/HLA)	human(A*66)
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.
QVPLRPMTYK had a significantly positive association with HLA A*66; it was recognized by 3/5 A*66-positive subjects and 3/212 A*66-negative subjects.

References

Displaying record number 57816

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef
Epitope	`QVPLRPMTYK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*08)
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 QVPLRPMTYK was recognized by 4/8 B*08-positive HIV-1-infected patients.

References

Displaying record number 976

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82 LAI)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B27)
Immunogen
Experimental methods
Keywords

Notes

Optimal epitope mapped by peptide titration.

References

CulmannPerCom B. Culmann. Personal communication, 1998. Show all entries for this paper.

Displaying record number 60069

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	QK10
Species (MHC/HLA)	human(B35:02, B35:03, B*53:01)
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.
QVPLRPMTYK had a significantly positive association with HLA B*3502,B*3503,B*5301; it was recognized by 10/25 B*3502,B*3503,B*5301-positive subjects and 10/225 B*3502,B*3503,B*5301-negative subjects.

References

Displaying record number 53346

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	QK10
Species (MHC/HLA)	human(B8)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Proliferation, Tetramer binding
Keywords	immunodominance, acute/early infection, characterizing CD8+ T cells

Notes

HIV-1 specific CD8+ T-cells in acute and long-term nonprogressive HIV-1 infection show strong ex-vivo proliferative capacities which are rapidly lost in chronic HIV-1 infection. The loss of CD8+ T-cell function is closely linked with the loss of HIV-1 specific, IL2 secreting CD4+ T-cells. The function can be rescued in vitro and in vivo by restoring the specific CD4+ T-cell help.
Full CD8+ T-cell responses to this epitope were dependent on co-stimulation with a CD4+ T cell dependent epitope from T-cells harvested during acute infection. The CD8+ T-cell response to this epitope was immunodominant in one study individual.

References

Lichterfeld2004 Mathias Lichterfeld, Daniel E. Kaufmann, Xu G. Yu, Stanley K. Mui, Marylyn M. Addo, Mary N. Johnston, Daniel Cohen, Gregory K. Robbins, Eunice Pae, Galit Alter, Alysse Wurcel, David Stone, Eric S. Rosenberg, Bruce D. Walker, and Marcus Altfeld. Loss of HIV-1-Specific CD8+ T Cell Proliferation after Acute HIV-1 Infection and Restoration by Vaccine-Induced HIV-1-Specific CD4+ T Cells. J. Exp. Med., 200(6):701-12, Sep 20 2004. PubMed ID: 15381726. Show all entries for this paper.

Displaying record number 55098

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location
Epitope	`QVPLRPMTYK`	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 QVPLRPMTYK 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.

Displaying record number 985

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

The anti-Nef CTL line P1 specific for this epitope is able to kill target cells via two mechanisms.
First: Ca²⁺-dependent, perforin-dependent Nef-specific lysis.
Second: Ca²⁺-independent, CD95-dependent apoptosis that could also kill non-specific targets.
Findings indicate that the two mechanisms are not mutually exclusive in human CTL, as they are in mice.
CTL mediated CD95-dependent apoptosis may play a role in pathogenesis.

References

Garcia1997 S. Garcia, M. Fevrier, G. Dadaglio, H. Lecoeur, Y. Riviere, and M.-L. Gougeon. Potential Deleterious Effect of Anti-Viral Cytotoxic Lymphocyte through the CD95 (FAS/APO-1)-Mediated Pathway during Chronic HIV Infection. Immunol. Lett., 57:53-58, 1997. PubMed ID: 9232425. Show all entries for this paper.

Displaying record number 61659

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HXB2 Location	Nef(73-82) DNA(9013..9042)	Nef Epitope Map
Author Location	Nef(73-82)
Epitope	`QVPLRPMTYK`	Epitope Alignment
Epitope Name	QK10
Subtype	B
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Patient MHC/HLA	AC1: A02:01, A30:01, B37:01, B38:01, C06:02, C12:03; VP1: A02:01, A03:01, B41:01, B52:01, C03:03, C17:01
Country	United States
Experimental methods	Other, Relative replication capacity assay
Keywords	NK cells, transmission pair

Notes

A transmission pair were studied to compare fitness of HIV isolates between the partners. Virus from both subjects were replication competent and transmissible. The female recipient of virus, subject AC1, did not have known protective HLA but protective KIR alleles and was a controller with <100 copies virus/ml during acute infection. Suppressive capacity of her CTLs did not change, but there was a marked decrease in NK cell reponse with the onset of viremic breakthrough at 9 months.
Nef (73-82) QK10, QVPLRPMTYK, was present in transmitting subject, VP1 and recipient pre- and post-loss of viremic control. No variant was detected. Presumed restricting allele was A*02.

References

Walker-Sperling2017 Victoria E. Walker-Sperling, Christopher W. Pohlmeyer, Rebecca T. Veenhuis, Megan May, Krystle A. Luna, Allison R. Kirkpatrick, Oliver Laeyendecker, Andrea L. Cox, Mary Carrington, Justin R. Bailey, Roberto C. Arduino, and Joel N. Blankson. Factors Associated with the Control of Viral Replication and Virologic Breakthrough in a Recently Infected HIV-1 Controller. EBioMedicine, 16:141-149, Feb 2017. PubMed ID: 28159573. Show all entries for this paper.