Search CTL/CD8+ T-Cell Epitope Database

Found 67 matching records:

Displaying record number 1776

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT(158-166)
Epitope	`AIFQSSMTK`	Epitope Alignment
Species (MHC/HLA)	human(A*03)
Immunogen	HIV-1 infection
Experimental methods
Keywords	rate of progression, acute/early infection

Notes

The CTL response to optimally defined CTL epitopes restricted by HLA class I A and B alleles in individuals who coexpressed HLA A*02, A*03, and B*07 was studied in eight HIV-1-infected subjects, two with acute infection, five with chronic, and one long-term non-progressor (LTNP)
2 to 17 epitopes were recognized in a given individual, A*02-restricted CTL response tended to be narrow and never dominated the response, and 25/27 epitopes were targeted by at least one person.
All patients recognized at least 1 A*03 epitope, up to 8 A*03 epitopes, but none was clearly dominant.
In two of the subjects, AIFQSSMTK was the dominant epitope.

References

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

Displaying record number 57045

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	ATK9
Species (MHC/HLA)	human(A*03)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, CTL neutralization assay, Chromium-release assay, Other
Keywords	elite controllers, neutralization by CTL

Notes

Relative antiviral efficacy of CD8 T-cell responses was assessed in a functional assay that measured the ability to neutralize virus in autologous CD4 T cells. CTL clones targeting diverse epitopes differed by >1000 fold in their ability to inhibit viral replication, despite similar EliSpot assay results. Cell lines stimulated with Gag epitopes neutralized HIV better than clones from the same person stimulated with Env epitopes. Greatest inhibition was observed with cell lines restricted by the protective HLA alleles B*27 and B*57.
An A3-ATK9-specific T-cell clone was isolated from an HIV-infected person. This clone responded to the ATK9 peptide in EliSpot and chromium release assays, but had poor antiviral function against 3 HIV isolates.

References

Chen2009a Huabiao Chen, Alicja Piechocka-Trocha, Toshiyuki Miura, Mark A. Brockman, Boris D. Julg, Brett M. Baker, Alissa C. Rothchild, Brian L. Block, Arne Schneidewind, Tomohiko Koibuchi, Florencia Pereyra, Todd M. Allen, and Bruce D. Walker. Differential Neutralization of Human Immunodeficiency Virus (HIV) Replication in Autologous CD4 T Cells by HIV-Specific Cytotoxic T Lymphocytes. J. Virol., 83(7):3138-3149, Apr 2009. PubMed ID: 19158248. Show all entries for this paper.

Displaying record number 59003

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol(101-)
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	Pol313
Subtype	A
Species (MHC/HLA)	human(A*03)
Immunogen	HIV-1 infection, vaccine
Country	Guinea-Bissau
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	vaccine-induced immune responses, vaccine antigen design, therapeutic vaccine, chronic infection

Vaccine Details

Vaccine type	peptide
Vaccine strain	A clade
Adjuvant	CAF01

Notes

Therapeutic vaccination of chronically infected HIV-1 subjects was evaluated as a means of halting disease progression. A subdominant peptide vaccine containing 15 CTL epitopes and 3 helper T-cell peptides along with an adjuvant was delivered to 18 infected subjects, and this Guinea-Bissau study compared to a similar Danish one. Using IFN-γ EliSpot, 9 new T-cell responses were detected in 6/14 subjects whose viral loads (VL) remained stable. Other pre-existing responses, including CTL responses, however, were not significantly detected.
Pol 313, AIFQSSMTK, is a CTL epitope sequence used as a vaccine component.

References

Roman2013 Victor Raúl Gómez Román, Kristoffer Jarlov Jensen, Sanne Skov Jensen, Christian Leo-Hansen, Sanne Jespersen, David da Silva Té, Candida Medina Rodrigues, Christoph Mikkel Janitzek, Lasse Vinner, Terese Lea Katzenstein, Peter Andersen, Ingrid Kromann, Lars Vibe Andreasen, Ingrid Karlsson, and Anders Fomsgaard. Therapeutic Vaccination Using Cationic Liposome-Adjuvanted HIV Type 1 Peptides Representing HLA-Supertype-Restricted Subdominant T Cell Epitopes: Safety, Immunogenicity, and Feasibility in Guinea-Bissau. AIDS Res Hum Retroviruses, 29(11):1504-1512, Nov 2013. PubMed ID: 23634822. Show all entries for this paper.

Displaying record number 59216

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol(325-333)
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	Pol 325-333
Subtype	B
Species (MHC/HLA)	human(A*03)
Immunogen	vaccine
Country	France
Experimental methods	CD8 T-cell Elispot - IFNγ, Degranulation, CD107a and b cell surface mobilization, Intracellular cytokine staining, Tetramer binding
Keywords	vaccine-induced immune responses

Vaccine Details

Vaccine type	lipopeptide

Notes

HIV-specific memory CTL responses from 16 lipopeptide-vaccinated uninfected unvaccinated subjects were fully characterized with respect to magnitude and multifunctionality, comparing them to FLU- or EBV-CTL. 62% of total secreting T cells produced IFN-γ in response to HIV (compared to 35% for FLU and EBV). HIV-specific CTL secreted either IFN-γ or TNF-α, not both as in FLU- and EBV-specific CTL. The more limited functional profile and magnitude of expanded CTL response against HIV mirrors its less effective vaccines.
Pol 325-333, AIFQSSMTK, lipopeptide was able to stimulate expanded effector CTLs that produced 163 SFC/10⁵ cells in EliSpot as opposed to none in 1 unvaccinated subject.

References

Figueiredo2014 Suzanne Figueiredo, Benedicte Charmeteau, Mathieu Surenaud, Dominique Salmon, Odile Launay, Jean-Gérard Guillet, Anne Hosmalin, and Hanne Gahery. Memory CD8+ T Cells Elicited by HIV-1 Lipopeptide Vaccines Display Similar Phenotypic Profiles but Differences in Term of Magnitude and Multifunctionality Compared with FLU- or EBV-Specific Memory T Cells in Humans. Vaccine, 32(4):492-501, 16 Jan 2014. PubMed ID: 24291199. Show all entries for this paper.

Displaying record number 59306

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	ATK9
Species (MHC/HLA)	human(A*03)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression

Notes

620 patients in early/acute stages of infection were screened for Elispot responses to optimally defined epitopes to find associations between specific CTL responses and long-term control of HIV-1. Seven epitope-specific responses were associated with delayed initiation of ART, and 12 were associated with a more rapid initiation of therapy. While initial viremia, HLA Class I genotype and viral set points were associated, breadth and magnitude of response did not influence early viral set point. A broader CTL response to Gag, however, associates with slower disease progression.
Initial specificity of CTL response rather than restricting HLA-I molecule contributes to disease control.
The HLA-A*03-restricted epitope AIFQSSMTK was associated with accelerated initiation of ART.

References

Streeck2014 Hendrik Streeck, Richard Lu, Noor Beckwith, Mark Milazzo, Michelle Liu, Jean-Pierre Routy, Susan Little, Heiko Jessen, Anthony D. Kelleher, Frederick Hecht, Rafick-Pierre Sekaly, Galit Alter, David Heckerman, Mary Carrington, Eric S. Rosenberg, and Marcus Altfeld. Emergence of Individual HIV-Specific CD8 T Cell Responses during Primary HIV-1 Infection Can Determine Long-Term Disease Outcome. J. Virol., 88(21):12793-12801, Nov 2014. PubMed ID: 25165102. Show all entries for this paper.

Displaying record number 62534

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol(313-321)
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	AK9
Subtype	B
Species (MHC/HLA)	human(A*03)
Immunogen	HIV-1 infection
Patient MHC/HLA	S00009: A03, A26, B15, B38, C03, C12
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	dynamics, chronic infection

Notes

This report analyzed 29 CTL responses against 23 HIV-1 epitopes in 9 untreated chronically infected "controllers" and identified inverse correlations between epitope variability and CTL clonal stability over time and between epitope variability and CTL clonal breadth.
Over 114 weeks, the AIFQSSMTK-specific CTL clonal response in individual S00009 demonstrated a 0.00 Sorenson similarity index and a mean breadth of 2.5 with a substantial degree of instability in clonal composition.
Based on all HIV-1 subtype B sequences in LANL HIV Sequence Database at time of analysis, GLNKIVRMY had a Simpson diversity index of 0.57.

References

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

Displaying record number 59538

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol(313-321)
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	ATK9
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.
AIFQSSMTK had a significantly positive association with HLA A*03; it was recognized by 21/63 A*03-positive subjects and 18/278 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 62730

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	ATK9
Species (MHC/HLA)	human(A*03)
Immunogen	in vitro stimulation or selection
Experimental methods	Chromium-release assay, In vitro proteasome digestion
Keywords	epitope processing

Notes

Cellular activation of CD4+ T cells affects the expression and activity of peptidases, the kinetics and patterns of in vitro degradation of Ags, and the endogenous processing of MHC-I HIV epitopes by HIV-infected CD4+ T cells which results in altered kinetics and efficiency of CTL recognition. When incubated with cytosolic extracts from activated CD4+ T cells, vs. resting CD4+ T cells, peptides were generally degraded more quickly with differential usages of specific sequence-based cleavage sites which resulted in fewer peptides containing intact epitopes.
When incubated with a synthetic 16mer, WKGSPAIFQSSMTKIL (5-ATK9-2), cytosolic extracts from CD3/CD28-stimulated CD4+ T cells, vs. from resting CD4+ T cells, produced less optimal CTL epitope AIFQSSMTK (ATK9), fewer precursors containing ATK9, and less 8-12mer peptides while producing more antitopes (a non-functional peptide that is generated by proteasomal cleavage within the epitope, resulting in partial overlaps with the functional epitope i.e. a peptide cleaved within the epitope) and fragments <7 aa long. AIFQSSMTK is known to be restricted to A*03:01/11:01.
In a chromium release assay with HLA-A03 ATK9-specific CTLs, the in vitro degradation products produced by CD3/CD28-stimulated CD4+ T-cell cytosolic extracts were significantly less antigenic than those produced by resting CD4+ T-cell cytosolic extracts and there was a positive correlation between the production of optimal ATK9 epitope and antigenicity.

References

Boucau2019 Julie Boucau, Julien Madouasse, Georgio Kourjian, Christopher S. Carlin, Daniel Wambua, Matthew J. Berberich, and Sylvie Le Gall. The Activation State of CD4 T Cells Alters Cellular Peptidase Activities, HIV Antigen Processing, and MHC Class I Presentation in a Sequence-Dependent Manner. J. Immunol., 202(10):2856-2872, 15 May 2019. PubMed ID: 30936293. Show all entries for this paper.

Displaying record number 53101

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT Pol(313-333)
Epitope	`AIFQSSMTK`	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, maintained T-helper cell responses. HIV-1 specific CD8+ T-cell responses were shown to increase significantly until the end of the follow up, but were not correlated with viral load.
5/14 patients recognized this epitope.

References

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

Displaying record number 58005

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	ATK9
Subtype	B
Species (MHC/HLA)	human(A03, A11)
Immunogen	in vitro stimulation or selection
Experimental methods	Chromium-release assay, Cytotoxicity assay, Other
Keywords	epitope processing

Notes

The cytosolic stability of 166 HIV-1 epitopes was found to be highly variable. Stability was correlated with antigenicity. Stability could be modulated through mutations, and some naturally-occurring mutations affect cytosolic stability and CTL recognition; reduced stability may be associated with escape.
A*03/A*11-ATK9 had intermediate stability in uninfected PBMC. In a cytotoxicity assay, cells loaded with ATK9 displayed limited lysis by epitope-specific CTLs.

References

Lazaro2011 Estibaliz Lazaro, Carl Kadie, Pamela Stamegna, Shao Chong Zhang, Pauline Gourdain, Nicole Y. Lai, Mei Zhang, Sergio A. Martinez, David Heckerman, and Sylvie Le Gall. Variable HIV Peptide Stability in Human Cytosol Is Critical to Epitope Presentation and Immune Escape. J. Clin. Invest., 121(6):2480-2492, Jun 2011. PubMed ID: 21555856. Show all entries for this paper.

Displaying record number 59125

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT(158-166 NL4.3)
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	ATK9
Subtype	B
Species (MHC/HLA)	human(A03, A11)
Immunogen	HIV-1 infected monocyte-derived
Country	United States
Experimental methods	Chromium-release assay, Other
Keywords	epitope processing, dendritic cells

Notes

Variations in HIV-1 peptide degradation pattern, kinetics, as well as production and degradation of HIV epitopes were correlated with cytosolic antigen-processing machinery of either monocyte-derived dendritic cells (DCs) or macrophages (MPs) after maturation with TRL4, TLR7/8 ligands. Generation of epitope precursors and epitopes from epitope-containing peptides was dependent on specific epitope and cytosolic extract type, leading to a 2- to 25-fold difference in CTL response in DCs, MPs and monocytes.
A synthetic 16-mer, WKGSPAIFQSSMTKIL, 5-ATK9-2, containing an A*03/A*11-restricted epitope AIFQSSMTK, ATK9, produced more ATK9 faster, along with N- and C- terminal extended versions as well as antitopes, when incubated with MP- rather than DC-cytosolic extracts.

References

Dinter2014 Jens Dinter, Pauline Gourdain, Nicole Y. Lai, Ellen Duong, Edith Bracho-Sanchez, Marijana Rucevic, Paul H. Liebesny, Yang Xu, Mariko Shimada, Musie Ghebremichael, Daniel G. Kavanagh, and Sylvie Le Gall. Different Antigen-Processing Activities in Dendritic Cells, Macrophages, and Monocytes Lead to Uneven Production of HIV Epitopes and Affect CTL Recognition. J. Immunol., 193(9):4322-4334, 1 Nov 2014. PubMed ID: 25230751. Show all entries for this paper.

Displaying record number 56383

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT(158-166)
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	AK9
Subtype	B
Species (MHC/HLA)	human(A03, A11)
Immunogen	HIV-1 infection
Country	Australia, Canada, Germany, United States
Experimental methods
Keywords	escape, HLA associated polymorphism

Notes

98 newly infected patients were studied to track early host HLA and Gag/Pol/Nef epitope immune responses' association with viral evolution. Response hierarchies were the same as those for later infection, and 50% of the most rapidly substituting epitopes were restricted by protective HLA, e.g. Gag B*57-associated mutations which were the most rapidly reverting upon transmission to a non-B*57-host. While there are great differences in mutation rates and reversions across the HIV proteome, most early viral change is driven by immune pressure.
HLA-driven epitope evolution was seen in 80% of published CTL epitopes.
HLAs-A*03 and A*11-associated substitution within optimally defined epitope AIFQSSMTK is at position K9, AIFQSSMTk. AK9 has a low recognition frequency and very low number of escapes.

References

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

Displaying record number 1118

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT(325-333)
Epitope	`AIFQSSMTK`	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 HLA A3 and reacted with this epitope 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 56195

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol(347-)
Epitope	`AIFQSSMTK`	Epitope Alignment
Species (MHC/HLA)	human(A*03:01)
Immunogen	vaccine
Country	Botswana, United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay
Keywords	vaccine antigen design

Vaccine Details

Vaccine type	DNA, polyepitope
Vaccine strain	multiple epitope immunogen

Notes

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

References

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

Displaying record number 448

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT(325-333)
Epitope	`AIFQSSMTK`	Epitope Alignment
Species (MHC/HLA)	human(A*03:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords	responses in children, mother-to-infant transmission

Notes

Epitope defined in the context of the Pediatric AIDS Foundation ARIEL Project, a mother-infant HIV transmission study.

References

Brander1995a Christian Brander and Bruce Walker. The HLA-Class I Restricted CTL Response in HIV-1 Infection: Identification of Optimal Epitopes. In The HLA-Class I Restricted CTL Response in HIV-1 Infection: Identification of Optimal Epitopes. pages IV--1--IV--9. Los Alamos National Laboratory, Theoretical Biology and Biophysics, Los Alamos, New Mexico, 1995. URL: http://hiv-web.lanl.gov/immunology. Show all entries for this paper.

Displaying record number 1116

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT(325-333 LAI)
Epitope	`AIFQSSMTK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*03:01)
Immunogen	HIV-1 infection
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 1117

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location
Epitope	`AIFQSSMTK`	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 55350

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT
Epitope	`AIFQSSMTK`	Epitope Alignment
Species (MHC/HLA)	human(A*03:01)
Immunogen
Experimental methods
Keywords

Notes

E169D is a processing mutation for HLA-B*0702 restricted SPAIFQSSM (SM9) as well as an epitope variation for HLA-A*0301 restricted MTKILEPFR (MR9).
Mutation 169D lies outside AIFQSSMTK. In vitro proteasome processing assays showed that both wild type or variant 27-mer synthetic peptide QGWKGSPAIFQSSMTKILE(d)PFRKQNPD released appropriate AIFQSSMTK-intermediate peptides within 6 h.

References

Zimbwa2007 Peter Zimbwa, Anita Milicic, John Frater, Thomas J. Scriba, Antony Willis, Philip J. R. Goulder, Tilly Pillay, Huldrych Gunthard, Jonathan N. Weber, Hua-Tang Zhang, and Rodney E. Phillips. Precise Identification of a Human Immunodeficiency Virus Type 1 Antigen Processing Mutant. J. Virol., 81(4):2031-2038, Feb 2007. PubMed ID: 17108020. Show all entries for this paper.

Displaying record number 52893

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	1339
Subtype	multiple
Species (MHC/HLA)	human(A03:01, A68:01, A11, A3, A33)
Immunogen	HIV-1 infection
Patient MHC/HLA	A2, A3, B51, B8, Cw1, Cw7; A26, A3, B52, B8; A11, A3, B14, B5, Cw8
Country	United States
Experimental methods	T-cell Elispot
Keywords	binding affinity, supertype, computational epitope prediction, HLA cross-presentation

Notes

Epitopes defined using sequence parsing and matching algorithm Conservatrix, and epitope prediction tool EpiMatrix, were shown to be conserved in a broad range of HIV-1 sequences derived from different parts of the world. 31 novel highly conserved HIV-1 epitopes were found, among which four were recognized as promiscuous epitopes and five as MHC supertypes.
Estimated binding probability for AIFQSSMTK: 59% Supertype epitope binding to A03, A3.1, A11, A6801, A33.

References

DeGroot2003 Anne S. De Groot, Bill Jesdale, William Martin, Caitlin Saint Aubin, Hakima Sbai, Andrew Bosma, Judy Lieberman, Gail Skowron, Fadi Mansourati, and Kenneth H. Mayer. Mapping Cross-Clade HIV-1 Vaccine Epitopes Using a Bioinformatics Approach. Vaccine, 21(27-30):4486-4504, 1 Oct 2003. PubMed ID: 14505932. Show all entries for this paper.

Displaying record number 53024

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol(325-333)
Epitope	`AIFQSSMTK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*03:01, A11, A33)
Immunogen	HIV-1 infection
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.
One of the patients responded to this peptide with GzB producing cells, while none of the patients 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 52428

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol
Epitope	`AIFQSSMTK`	Epitope Alignment
Subtype	A, B, C, D
Species (MHC/HLA)	human, macaque(A*03:01, A11, A33)
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 446

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT(325-333)
Epitope	`AIFQSSMTK`	Epitope Alignment
		Show epitope variants
Species (MHC/HLA)	human(A03:01, A11:01, A*68:01, A3)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

Study of the fine specificity of an A3-like super-type epitope (the A3 super-type includes A*0301, A*1101, A*3101, A*3301, and A*6801)
A3 super-type is characterized by a hydrophobic or hydroxyl containing anchor residue at position 2, and a positive charge in the C-term position.
While most lines were specific, promiscuous cloned CTL lines were also derived from HIV+ donors that could recognize epitope presented by either A3 or A11 or A*6801.
Alanine substitutions throughout the epitope and natural variants indicate that the same amino acid positions are critical for presentation by either MHC molecule, A*03 or* A11.
AIFQSSMTK is presented by three members of the A3 superfamily: A*0301, A*1101, and A*6801, and the naturally occurring variants A1S and K9R are recognized with similar efficiency to wild type epitope -- AIFQRSMTR can also bind to two additional members of the A3 superfamily, A*3101 and A*3301.

References

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

Threlkeld1997 S. C. Threlkeld, P. A. Wentworth, S. A. Kalams, B. M. Wilkes, D. J. Ruhl, E. Kepgh, J. Sidney, S. Southwood, B. D. Walker, and A. Sette. Degenerate and Promiscuous Recognition by CTL of Peptides Presented by the MHC Class I A3-Like Superfamily. J. Immunol., 159(4):1648-1657, 1997. Similarities in peptide binding across A3-like superfamily results in similar peptide-MHC complex structures engaged by T-cell receptors. PubMed ID: 9257824. Show all entries for this paper.

Displaying record number 1500

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT(325-333 LAI)
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	P3
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 1741

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol(305-313 93TH253 subtype CRF01)
Epitope	`AIFQSSMTK`	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.
6/8 tested FSWs recognized this epitope.
An HLA-A*11 tetramer was made for this epitope, which was recognized by two subjects -- and both subjects had expanded tetramer staining T-cell populations 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 59537

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol(313-321)
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	ATK9
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.
AIFQSSMTK had a significantly positive association with HLA A*11; it was recognized by 13/28 A*11-positive subjects and 5/250 A*11-negative subjects.

References

Displaying record number 59191

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT(158-166 NL4.3)
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	ATK9
Subtype	B
Species (MHC/HLA)	human(A*11)
Immunogen	HIV-1 infection
Experimental methods	In vitro proteasome digestion, Other
Keywords	epitope processing

Notes

7 HIV protease inhibitors (PIs) were shown to alter not only proteasome but also aminopeptidase activities that generate epitopes for MHC presentation. These inhibitors altered degradation patterns, sensitivity of peptides to degradation, kinetics and amounts of epitope production and therefore recognition by CTLs.
Half life of A*11-restricted ATK9, AIFQSSMTK, was unchanged by PIs. Killing by ATK9-specific CTL in presence of Saquinavir, Ritonavir, Nelfinavir and Indinavir was reduced.

References

Kourjian2014 Georgio Kourjian, Yang Xu, Ijah Mondesire-Crump, Mariko Shimada, Pauline Gourdain, and Sylvie Le Gall. Sequence-Specific Alterations of Epitope Production by HIV Protease Inhibitors. J. Immunol., 192(8):3496-3506, 15 Apr 2014. PubMed ID: 24616479. Show all entries for this paper.

Displaying record number 52068

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT(158-166 IIIB)
Epitope	`AIFQSSMTK`	Epitope Alignment
		Show epitope variants
Subtype	B
Species (MHC/HLA)	human(A11)
Immunogen	HIV-1 infection
Experimental methods
Keywords	epitope processing, escape

Notes

HIV polymorphisms in the RT protein were examined relation to HLA alleles found in a population of 473 participants in the Western Australian HIV Cohort Study. 64 significant associations between polymorphisms at particular positions and HLA alleles were detected, for HLA-B7, -B12, -B35 and -B15. Fifteen of these were in positions with known epitopes, 4 in anchor residues, 11 in other positions. Six additional polymorphic sites associated with particular HLA molecules flanked known epitopes and may relate to processing.
HLA-A11+ individuals with a K166x (4/19) substitution had higher viral loads than those that did not, suggesting escape was associated with diminished immune control of viremia.

References

Moore2002b Corey B. Moore, Mina John, Ian R. James, Frank T. Christiansen, Campbell S. Witt, and Simon A. Mallal. Evidence of HIV-1 adaptation to HLA-restricted immune responses at a population level. Science, 296(5572):1439-1443, 24 May 2002. PubMed ID: 12029127. Show all entries for this paper.

Displaying record number 1721

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol(305-313 93TH253 subtype CRF01)
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	P313-321
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 the HEPS study subject 128 who was HLA A11/A33.
This epitope was strongly reactive in HIV+ study subjects 053 and 184 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 53479

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol(314-322)
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	AK9
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 one of the escape variants, a novel CD8 T-cell response equal in magnitude to the wild type, was generated. CD8 T-cell recognizing the variant epitope utilized a distinct T-cell receptor and did not exhibit any cross-reactivity against the wild type.
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 449

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT(325-333 LAI)
Epitope	`AIFQSSMTK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A11)
Immunogen	peptide-HLA interaction
Experimental methods
Keywords

Notes

Exploration of A11 binding motif, based on Nixon et al. 1991.

References

Zhang1993 Q.-I. Zhang, R. Gavioli, G. Klein, and M. G. Masucci. An HLA-A11-Specific Motif in Nonamer Peptides Derived from Viral And Cellular Proteins. Proc. Natl. Acad. Sci. U.S.A., 90:2217-2221, 1993. PubMed ID: 8384718. Show all entries for this paper.

Displaying record number 53558

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol(314-322)
Epitope	`AIFQSSMTK`	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 53752

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol(313-321)
Epitope	`AIFQSSMTK`	Epitope Alignment
		Show epitope variants
Epitope Name	AK9
Subtype	B
Species (MHC/HLA)	human(A11)
Immunogen	HIV-1 infection
Patient MHC/HLA	A01, A11, B08, B15, C04, C07
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, Flow cytometric T-cell cytokine assay
Keywords	escape, optimal epitope

Notes

HIV-1-specific CD8 T-cell responses were persistent in the chronic phase of HIV-1 infection, although the responses to some of the epitopes declined despite the persistence of the targeted sequences in vivo. Only 4/14 epitopes were potential CTL escape variants, although strong responses to these epitopes persisted for 6 years. This indicates limited viral evolution within targeted CD8 T-cell epitopes during the chronic phase of infection.
The AK9 variant AIFQSSMTr was essentially the only form of the epitope detected over a 5-year period in this person. Elispot reactions indicated the T-cell clones only recognized the autologous form, not the B clade consensus, AIFQSSMTK. Two rare variants were observed at the 5-year time point, tIFQSSMTr and AIFQSSMar.

References

Koibuchi2005a Tomohiko Koibuchi, Todd M. Allen, Mathias Lichterfeld, Stanley K. Mui, Kristin M. O'Sullivan, Alicja Trocha, Spyros A. Kalams, R. Paul Johnson, and Bruce D. Walker. Limited Sequence Evolution within Persistently Targeted CD8 Epitopes in Chronic Human Immunodeficiency Virus Type 1 Infection. J. Virol., 79(13):8171-8181, Jul 2005. PubMed ID: 15956562. Show all entries for this paper.

Displaying record number 54260

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	A11-AK9 (RT)
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 445

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT
Epitope	`AIFQSSMTK`	Epitope Alignment
Species (MHC/HLA)	human(A11)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

CTL specific for HIV epitopes were used to show that the mediators of both the cytolytic (granzyme A was used as the marker) and non-cytolytic (HIV-1 inhibitory chemokines MIP-1 α and RANTES were used as markers) anti-viral responses are localized within the CTL's cytotoxic granules.

References

Wagner1998b L. Wagner, O. O. Yang, E. A. Zepeda, Y. Ge, S. A. Kalams, B. D. Walker, M. S. Pasternack, and A. D. Luster. Beta-Chemokines Are Released from HIV-1-Specific Cytolytic T Cell Granules Complexed to Proteoglycans. Nature, 391:908-911, 1998. PubMed ID: 9495345. Show all entries for this paper.

Displaying record number 450

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT(325-333 LAI)
Epitope	`AIFQSSMTK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A11)
Immunogen	HIV-1 infection
Experimental methods
Keywords	review

Notes

Review of HIV CTL epitopes.

References

McMichael1994 A. J. McMichael and B. D. Walker. Cytotoxic T Lymphocytes Epitopes: Implications for HIV Vaccine. AIDS, 8S:S155-S173, 1994. Comprehensive review summarizing CTL epitopes that have known HLA type and are fine mapped to indicate epitope boundaries. Anchor residues are indicated when known for different HLA restricted epitopes. Includes a summary of the published literature, as well as much work that was in press or submitted for publication. Show all entries for this paper.

Displaying record number 1429

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol(313-321)
Epitope	`AIFQSSMTK`	Epitope Alignment
Species (MHC/HLA)	human(A11, A3)
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 57829

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	ATK9
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.
AIFQSSMTK was one of 20 optimal epitopes tested.

References

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

Displaying record number 53350

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT( B consensus)
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	ATK9
Species (MHC/HLA)	human(A11, A3)
Immunogen	HIV-1 infection
Patient MHC/HLA	A11, A2, B18, B44, C*12, Cw5; A3, B14, B60, Cw3, Cw7; A1, A3, B14, B8, Cw7, Cw8
Country	United States
Experimental methods	Chromium-release assay, Cytokine production, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords	HLA cross-presentation, 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.
3/9 individuals recognized this epitope, two presented by HLA-A3, one presented by HLA-A11.

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 1654

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol(325-333)
Epitope	`AIFQSSMTK`	Epitope Alignment
Species (MHC/HLA)	human(A11, A3, A33)
Immunogen	HIV-1 exposed seronegative, HIV-1 infection
Experimental methods
Keywords	HIV exposed persistently seronegative (HEPS)

Notes

Variants (S/A)IFQSSMTK are specific for the A/B clades.
ELISPOT was used to study CTL responses to a panel of 54 predefined HIV-1 epitopes in 91 HIV-1-exposed, persistently seronegative (HEPS) and 87 HIV-1-infected female Nairobi sex workers.
Responses in HEPS women tended to be lower, and focused on different epitopes with HLA presenting molecules that have previously been associated with reduced risk of infection, and there was a shift in the response in the HEPS women upon late seroconversion to epitopes recognized by the HIV-1 infected women.
43/91 HEPS women had CD8+ responses and detection of HIV-1-specific CTL in HEPS women increased with the duration of viral exposure.
Among HLA-A3 women, 2/2 HEPS and 3/3 HIV-1 infected women recognized this epitope.
The dominant response to this HLA allele was to this epitope in one of the 2/2 HEPS cases and in one of the 3/3 HIV-1 infected women.

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 54959

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol(325-333)
Epitope	`AIFQSSMTK`	Epitope Alignment
Species (MHC/HLA)	(A11, A3, A33, A68)
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 61818

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	AK9
Species (MHC/HLA)	human(A*11:01)
Immunogen	HIV-1 infection, vaccine
Patient MHC/HLA	VID421: A02:01, A11:01, B35:03, B40:02, C02:02, C12:03
Country	United Kingdom
Experimental methods	Intracellular cytokine staining, Other
Keywords	vaccine-induced immune responses, optimal epitope

Notes

Since CTL response in natural HIV-1 infections is mostly against variable but immunodominant epitopes, lymphocytes from 12 vaccine(HIVconsv)-exposed subjects of the HIV-CORE 002 study were used to determine and define 14 less variable but typically subdominant, optimal novel epitopes.
Epitope AIFQSSMTK (AK9) is within peptide GSPAIFQSSMTKILE (HC088) that was recognized by VID421, 1/12 vaccinated subjects. AK9 is restricted by HLA-A*1101 in this subject is an A-list epitope in the Los Alamos HIV Immunology database.

References

Borthwick2017 Nicola Borthwick, Zhansong Lin, Tomohiro Akahoshi, Anuska Llano, Sandra Silva-Arrieta, Tina Ahmed, Lucy Dorrell, Christian Brander, Hayato Murakoshi, Masafumi Takiguchi, and Tomáš Hanke. Novel, In-Natural-Infection Subdominant HIV-1 CD8+ T-Cell Epitopes Revealed in Human Recipients of Conserved-Region T-Cell Vaccines. PLoS One, 12(4):1-19, 2017. PubMed ID: 28448594. Show all entries for this paper.

Displaying record number 1126

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT(325-333 LAI)
Epitope	`AIFQSSMTK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*11:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords	optimal epitope, A-list

Notes

C. Brander notes this is an A*1101 epitope.

References

Displaying record number 52099

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol(313-321)
Epitope	`AIFQSSMTK`	Epitope Alignment
Subtype	B, CRF01_AE
Species (MHC/HLA)	human(A*11:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords	subtype comparisons

Notes

Counterparts for eight known clade B HLA A*1101 epitopes were generated for clade E (CRF01). Three epitopes, identical among clade A-E, were cross-reactive and recognized by clade E infected individuals. The clade E and B analogs to three more HLA A*1101 epitopes was recognized in a clade specific manner. Two other HLA A*1101 clade B defined epitopes were found not to have stimulated a response in clade E infected individuals.
AIFQSSMTK is commonly found in viruses representing subtypes A-E. It was strongly recognized by CTL from 2/5 B clade infected Japanese subjects, and 5/6 E clade infected Thai subjects.

References

Fukada2002 Katsuhiko Fukada, Hiroko Tomiyama, Chantapong Wasi, Tomoko Matsuda, Shigeru Kusagawa, Hironori Sato, Shinichi Oka, Yutaka Takebe, and Masafumi Takiguchi. Cytotoxic T-cell Recognition of HIV-1 Cross-Clade and Clade-Specific Epitopes in HIV-1-Infected Thai and Japanese Patients. AIDS, 16(5):701-711, 29 Mar 2002. PubMed ID: 11964526. Show all entries for this paper.

Displaying record number 53048

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT(313-321)
Epitope	`AIFQSSMTK`	Epitope Alignment
Subtype	B, CRF01_AE
Species (MHC/HLA)	human(A*11:01)
Immunogen
Country	Thailand
Experimental methods
Keywords	HIV exposed persistently seronegative (HEPS), 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 61328

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	AK9
Subtype	A, B, C, D
Species (MHC/HLA)	human(A*11:01)
Immunogen	vaccine
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Other
Keywords	vaccine-induced immune responses, immunodominance

Notes

Previous studies of the HIVconsv vaccine containing a chimeric protein with alternating HIV-1 Clade A, B, C, D conserved regions showed that subdominant epitopes could induce strong CTL response correlating with Gag and Pol-specific IFN-γ production. Here the specificity i.e. the epitopes themselves were characterized as well as the functionality, (i.e. cytokine production) of CTL from 3 subjects of the HIV-CORE 002 trial.
CTL elicited by HIVconsv from healthy human volunteer 421 (A*0201, A*1101/ B*3503, B*4002/ Cw*0202, Cw*1203) when expanded upon stimulation with peptide Pol 88, GSPAIFQSSMTKILE (Pol 311-325), gave a strongly hierarchical immune response of a maximum of 2017 sfc/ml. It contained the mapped epitope AIFQSSMTK.

References

Ahmed2016 Tina Ahmed, Nicola J. Borthwick, Jill Gilmour, Peter Hayes, Lucy Dorrell, and Tomáš Hanke. Control of HIV-1 Replication In Vitro by Vaccine-Induced Human CD8+ T Cells through Conserved Subdominant Pol Epitopes. Vaccine, 34(9):1215-1224, 24 Feb 2016. PubMed ID: 26784683. Show all entries for this paper.

Displaying record number 61875

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	AK9
Subtype	B
Species (MHC/HLA)	human(A*11:01)
Immunogen	HIV-1 infection, vaccine
Country	Japan
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Other
Keywords	vaccine-induced immune responses

Notes

The candidate tHIVconsvX vaccine is composed of 6 conserved Gag and Pol regions. Specific T cells - from 200 ART-naive, infected Japanese subjects previously exposed to the tHIVconsvX vaccine - that have the ability to supress HIV-1 replication were identified as recognizing 6 Pol epitopes. 6/25 epitopes (comprising 20 known and 5 novel mapped epitopes) remain associated with positive clinical outcome.
A*1101-restricted Pol epitope AIFQSSMTK was found in 15-mer peptide pair C246/247. While 4/221 Japanese subjects responded to the epitope, 2/20 HLA-carrying tested responders reacted to this epitope in EliSpot.

References

Zou2019 Chengcheng Zou, Hayato Murakoshi, Nozomi Kuse, Tomohiro Akahoshi, Takayuki Chikata, Hiroyuki Gatanaga, Shinichi Oka, Tomáš Hanke, and Masafumi Takiguchi. Effective Suppression of HIV-1 Replication by Cytotoxic T Lymphocytes Specific for Pol Epitopes in Conserved Mosaic Vaccine Immunogens. J. Virol., 93(7), 1 Apr 2019. PubMed ID: 30674626. Show all entries for this paper.

Displaying record number 56538

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	Pol347
Subtype	B
Species (MHC/HLA)	human(A3)
Immunogen	vaccine
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	vaccine antigen design

Vaccine Details

Vaccine type	DNA, polyepitope
Vaccine component	other

Notes

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

References

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

Displaying record number 54252

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	A3-ATK9(RT)
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 53503

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	AK9
Subtype	B
Species (MHC/HLA)	human(A3)
Immunogen	HIV-1 infection
Patient MHC/HLA	A1, A3, B57, B7, Cw6, Cw7
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	subtype comparisons, escape, characterizing CD8+ T cells, viral fitness and reversion

Notes

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

References

Displaying record number 58417

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	Pol313
Subtype	B, CRF02_AG
Species (MHC/HLA)	human(A3)
Immunogen	HIV-1 infection
Country	Cote D'Ivoire, Denmark, Ghana, Guinea-Bissau, Mali, Senegal
Experimental methods	Intracellular cytokine staining, Pentamer labeling
Keywords	vaccine antigen design

Notes

15 subdominant CTL epitopes were used to study 2 new Guinea-Bissau HIV-1 isolates, a newly completed Danish subtype B genome sequence and other previously published West African sequences. Subtype analysis showed the 2 new Guinea-Bissau sequences were CRF02_AG inter-subtype recombinant forms with typical cross-over points. The 15 epitopes were restricted by common HLA alleles (A1, A2, A3, B7, B44) and were present and conserved in all sequences studied. Mean conservation of the epitopes in local strains was 76% and 70% for Denmark and West Africa respectively. All epitopes had been previously confirmed as antigenic [Perez2008].
Pol313 epitope, AIFQSSMTK, showed a conservation of amino acid identity of 89% for the Danish sequence and 40% for the West African sequences.

References

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

Vinner2011 Lasse Vinner, Birgitta Holmgren, Kristoffer J. Jensen, Joakim Esbjornsson, Marie Borggren, Julie L. Hentze, Ingrid Karlsson, Betina S. Andresen, Gregers J. Gram, Henrik Kloverpris, Peter Aaby, Zacarias José Da Silva, Eva-Maria Fenyö, and Anders Fomsgaard. Sequence Analysis of HIV-1 Isolates from Guinea-Bissau: Selection of Vaccine Epitopes Relevant in Both West African and European Countries. APMIS, 119(8):487-497, Aug 2011. PubMed ID: 21749448. Show all entries for this paper.

Displaying record number 52974

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT(158-166)
Epitope	`AIFQSSMTK`	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 52826

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT(158-166)
Epitope	`AIFQSSMTK`	Epitope Alignment
		Show epitope variants
Epitope Name	A3-AK9 Pol
Subtype	B
Species (MHC/HLA)	human(A3)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	supervised treatment interruptions (STI), escape, early treatment, superinfection

Notes

An HIV+ individual given acute ARV and undergoing STI developed a strong CTL immune response, but despite this was shown to be superinfected with second B clade virus. Some epitope variants of the second infecting virus were resistant to the initial CTL response.
The second infecting strain had the variant aifqssmIk. The CTL response to the second variant was zero or low at all timepoints. The CTL response to the first variant was also low, and declined over time.

References

Altfeld2002a Marcus Altfeld, Todd M. Allen, Xu G. Yu, Mary N. Johnston, Deepak Agrawal, Bette T. Korber, David C. Montefiori, David H. O'Connor, Ben T. Davis, Paul K. Lee, Erica L. Maier, Jason Harlow, Philip J. R. Goulder, Christian Brander, Eric S. Rosenberg, and Bruce D. Walker. HIV-1 Superinfection Despite Broad CD8+ T-Cell Responses Containing Replication of the Primary Virus. Nature, 420(6914):434-439, 28 Nov 2002. PubMed ID: 12459786. Show all entries for this paper.

Displaying record number 52146

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT Pol(313-321)
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	A3-ATK9
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.
0/14 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. 3/7 individuals began to have 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 1524

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT(325-333 SF2)
Epitope	`AIFQSSMTK`	Epitope Alignment
Species (MHC/HLA)	human(A3)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART, acute/early infection

Notes

Therapy provided during acute infection resulted in a narrower CTL response, stronger T help response, and a less diverse viral population than was seen in individuals treated during chronic infection.
The breadth and specificity of the response was determined using ELISPOT by studying 19 individuals with pre-seroconversion therapy (Group 1), 11 individuals with primary infection but post-seroconversion therapy (Group 2), and 10 individuals who responded to HAART given during chronic infection (Group 3), using 259 overlapping peptides spanning p17, p24, RT, gp41, gp120 and Nef.
Previously described and newly defined optimal epitopes were tested for CTL response.
Number of HLA-A3+ individuals that had a CTL response to this epitope broken down by group: 0/7 group 1, 0/4 group 2, and 1/2 group 3.

References

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

Displaying record number 452

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol(325-333 IIIB)
Epitope	`AIFQSSMTK`	Epitope Alignment
		Show epitope variants
Species (MHC/HLA)	human(A3)
Immunogen	HIV-1 infection
Experimental methods
Keywords	responses in children, mother-to-infant transmission, escape

Notes

This study describes maternal CTL responses in the context of mother-to-infant transmission.
Detection of CTL escape mutants in the mother was associated with transmission, but the CTL-susceptible forms of the virus tended to be found in infected infants.
One variant found in an infant gave a positive CTL response: AIFQSSMTR.
AIFLSSMTK and TISQSSMTK were escape mutants.

References

Wilson1999a C. C. Wilson, R. C. Brown, B. T. Korber, B. M. Wilkes, D. J. Ruhl, D. Sakamoto, K. Kunstman, K. Luzuriaga, I. C. Hanson, S. M. Widmayer, A. Wiznia, S. Clapp, A. J. Ammann, R. A. Koup, S. M. Wolinsky, and B. D. Walker. Frequent Detection of Escape from Cytotoxic T-Lymphocyte Recognition in Perinatal Human Immunodeficiency Virus (HIV) Type 1 Transmission: The Ariel Project for the Prevention of Transmission of HIV from Mother to Infant. J. Virol., 73:3975-3985, 1999. PubMed ID: 10196293. Show all entries for this paper.

Displaying record number 444

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT(325-333 IIIB)
Epitope	`AIFQSSMTK`	Epitope Alignment
Species (MHC/HLA)	human(A3)
Immunogen	HIV-1 infection
Experimental methods
Keywords	responses in children, mother-to-infant transmission

Notes

Epitope defined in the context of the Pediatric AIDS Foundation ARIEL Project, a mother-infant HIV transmission study.
AIFQSSMTR and AILQSSMTK, naturally occurring variants, were found in infant, and are recognized.
TISQSSMTK, a naturally occurring variant, was found in infant and is not recognized.

References

Walkerpercom1996 C. Wilson, B. Wilkes, D. Ruhl, and B. Walker. Personal communication, 1996. Defined in the context of the Pediatric AIDS Foundation ARIEL Project, a mother-infant HIV transmission study. Personal communication. Show all entries for this paper.

Displaying record number 447

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT(325-333 LAI)
Epitope	`AIFQSSMTK`	Epitope Alignment
		Show epitope variants
Subtype	B
Species (MHC/HLA)	human(A3)
Immunogen	HIV-1 infection
Experimental methods
Keywords	subtype comparisons

Notes

The consensus peptide of B and D clade viruses is AIFQSSMTK.
The consensus peptide of a subset of As is AIFQASMTK and it is less able to stimulate the CTL clone.
The consensus peptide of a subset of As is SIFQSSMTK and is as reactive as the originally defined epitope.

References

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

Displaying record number 451

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT(325-333 LAI)
Epitope	`AIFQSSMTK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A33)
Immunogen
Experimental methods
Keywords

Notes

Defined as minimal peptide by titration curve, S. Rowland-Jones, pers. comm.
Database note: Author "Rowland-Jones" is also found as "RowlandJones" on annotated papers in this database.

References

Rowland-JonesPerCom1995 S. Rowland-Jones. Personal communication, 1995. Show all entries for this paper.

Displaying record number 1331

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location
Epitope	`AIFQSSMTK`	Epitope Alignment
Species (MHC/HLA)	human(A33)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HIV exposed persistently seronegative (HEPS)

Notes

This study examines CTL responses in HIV exposed, persistently seronegative individuals, HEPS, who eventually seroconverted -- 11/114 HEPS Nairobi sex workers eventually seroconverted, and for six of these HIV CTL reactive epitopes had been defined while seronegative.
The epidemiological factor associated with seroconversion was stopping sex work. HIV-specific CTL activity declined when HEPS sex workers stopped working for a period or retired.
This epitope was recognized in 1/22 HEPS sex worker controls, ML1668.

References

Kaul2001 R. Kaul, S. L. Rowland-Jones, J. Kimani, T. Dong, H. B. Yang, P. Kiama, T. Rostron, E. Njagi, J. J. Bwayo, K. S. MacDonald, A. J. McMichael, and F. A. Plummer. Late Seroconversion in HIV-Resistant Nairobi Prostitutes Despite Pre-Existing HIV-Specific CD8+ Responses. J. Clin. Invest., 107(3):341-349, Feb 2001. URL: http://www.jci.org/cgi/content/full/107/3/341. PubMed ID: 11160158. Show all entries for this paper.

Displaying record number 56517

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	Pol347
Subtype	A, B, C, D
Species (MHC/HLA)	human, mouse(A3 supertype)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	binding affinity, supertype, vaccine-induced immune responses, HLA cross-presentation

Notes

21 supertype-A2, -A3 and -B7-restricted epitopes predicted to be immunogenic by HLA-peptide binding motifs and phenotypic frequency in individuals were recognized by HIV-1+ subjects in ELISpot assays and shown to bind with high affinity to minimum 3 HLA-alleles of the restricting supertype. These epitopes were included in DNA vaccine EP HIV-1090 that avoided immunodominant responses and did not restrict subject immunity to predicted HLA-type when tested in mice. Transgenic mice mounted a vaccine-response similar to that induced by ELISpot assay in humans.
Epitope AIFQSSMTK of the HLA-A3 supertype bound most strongly to HLA-A*1101, and -A*0301 and also to -A*6801 but not to -A*3301 or A-*3101. It was conserved 25% in subtype A, 79% in B, 25% in C and 75% in subtype D. 3/23 HLA-A3 supertype expressing HIV-1+ subjects mounted a positive ELISpot response to Pol347.

References

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

Displaying record number 1615

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol(337-345)
Epitope	`AIFQSSMTK`	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 55540

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT(158-166)
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	AK9
Subtype	B
Species (MHC/HLA)	human(A*68:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	A1, A68:01, B51, B8, C15, Cw7, DQ2, DQ3, DR3, DR4
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, escape, mutation acquisition

Notes

An LTNP was followed longitudinally over 6 years and 3 sampling time points, until transition to disease. His HLA were heterozygous and not associated with nonprogressive infection, but 3 alleles were associated with poor clinical prognosis. No attenuating mutations in initial samplings, but an insertion in the V2 loop and continuing CCR5 coreceptor use were found.
A decrease in IFN-gamma response was seen over time, suggesting CTL dysfunction. An increase in T-cell epitopes targeted (e.g. emergence of YL8, YLKDQQLL and WY20, WKFDSRLAFHHMARELHPEY variants and gain of response to EL9, EIKDTKEAL, NL10, NSNPDCKTIL, AK9, AIFQSSMTK, WM8, WSMVRERM, VT15, WVHHTQGYFPDWQNYT) was seen concomitant with disease progression, reflecting viral replication and/or variants.
HLA-A*6801-restricted autologous epitope AIFQSSMTK was able to elicit CTL response only by the last time point. HLA restriction was predicted in this study based on the patient's HLA alleles and previous publication.

References

Kemal2008 Kimdar Sherefa Kemal, Tara Beattie, Tao Dong, Barbara Weiser, Rupert Kaul, Carla Kuiken, Julian Sutton, Dorothy Lang, Hongbing Yang, Yan Chun Peng, Ronald Collman, Sean Philpott, Sarah Rowland-Jones, and Harold Burger. Transition from Long-Term Nonprogression to HIV-1 Disease Associated with Escape from Cellular Immune Control. J. Acquir. Immune Defic. Syndr., 48(2):119-126, 1 Jun 2008. PubMed ID: 18520675. Show all entries for this paper.

Displaying record number 62876

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HXB2 Location	Pol(313-321) RT(158-166)	Pol Epitope Map
Author Location	RT(158-166)
Epitope	`AIFQSSMTK`	Epitope Alignment
		Show epitope variants
Epitope Name	AK9
Subtype	B, C
Species (MHC/HLA)	human
Immunogen	HIV-1 infection, engineered
Experimental methods	Other, Relative replication capacity assay
Keywords	structure, vaccine antigen design

Notes

Single nucleotide mutations were introduced onto a patient-derived subtype C reverse transciptase (RT)-integrase sequence (SK-278, 98.2% similar to Con C) on a subtype B NL4-3ΔRT-integrase backbone and assessed for their impact on <i>in vitro</i> viral replicative capacity (RC) in a GFP-based assay. Structural modeling of the RT mutations that mediated the greatest RC reductions (A158S, V241I, & I257V) provided insight into functional consequences.
Relative to NL4-3 recombinant virus encoding wild-type SK-278 RT-integrase, the introduction of RT mutation A158S mediated ˜10% reduction in RC.
A158S is located in the β-α helix E loop near the RT fingers & palm subdomains, as well as the catalytic site. Structural modeling identified altered distances between A158S, key residues and β5a strand, as well as a hydrogen bond with catalytic site residue G155, that may affect RT function.
A158S is located within best-defined epitope AIFQSSMTK (AK9, known to bind to A*03:01/A*11:01), as well as in overlapping epitopes LPQGWKGSPA & SPAIFQSSM, which are all present in SK-278.

References

Ojwach2021 Doty B. A. Ojwach, Paradise Madlala, Michelle Gordon, Thumbi Ndung'u, and Jaclyn K. Mann. Vulnerable targets in HIV-1 Pol for attenuation-based vaccine design. Virology, 554:1-8 doi, Feb 2021. PubMed ID: 33316731 Show all entries for this paper.

Displaying record number 56955

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol
Epitope	`AIFQSSMTK`	Epitope Alignment
Subtype	B, C
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	Sweden
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	subtype comparisons, computational epitope prediction, vaccine antigen design

Notes

From HIV-1 sequences of multiple subtypes, bioinformatic prediction generated 174 CTL epitopes from Gag, Pol, Nef, Env and Tat restricted by HLA supertypes A1, A2, A3, A24, B7, B44 and B58; 10 previously-published A2- and B58-restricted epitopes were also included. Of these 184 epitopes, 113 were recognized experimentally in serum from 31 HIV+ patients.
While Gag, Pol, Env and Nef were highly immunogenic, only 38% of Tat epitopes elicited a response.
AIFQSSMTK was a predicted epitope restricted by A3 supertype. 2/31 patient(s) responded to it; both were known to carry an allele of A3 supertype. Responding patients were infected with HIV clade(s) B, C.

References

Displaying record number 58064

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol
Epitope	`AIFQSSMTK`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human
Immunogen	vaccine
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	vaccine-induced immune responses

Vaccine Details

Vaccine type	adenovirus type 5 (Ad5), DNA prime with Ad5 boost
Vaccine strain	B clade IIIB, B clade JRFL, B clade CAM-1
Vaccine component	Gag, Nef, Pol

Notes

T-cell epitope response specificities were examined in uninfected subjects who received the Gag/Pol/Nef vaccine used in the Step trial. Variable epitopes were detected more frequently than would be expected from an unbiased sampling. The most conserved epitopes were detected at a lower frequency, similar to the frequency reported for responses to natural infection, suggesting potential epitope masking. This may be a mechanism used by the virus in both contexts to escape effective T-cell surveillance. Development of vaccine strategies that can elicit a greater breadth, and towards conserved regions of the genome in particular, are critical requirements for effective T-cell based vaccines.
All vacinees had responses to the Gag peptide pool, and most also had responses to the Nef and/or Pol pools. Subsequent mapping using 9mer minipools demonstrated that T-cell epitopes were recognized across the length of all 3 proteins. A total of 105 distinct 9mers were detected, although some of these may have been overlapping 9mers representing a single epitope.
3 vaccinees recognized 9mer AIFQSSMTK.
Database note: The HLA restriction of this epitope in the LANL database is A3/A11, and all 3 responders were A3/A11-positive.

References

Li2011a Fusheng Li, Adam C. Finnefrock, Sheri A. Dubey, Bette T. M. Korber, James Szinger, Suzanne Cole, M. Juliana McElrath, John W. Shiver, Danilo R. Casimiro, Lawrence Corey, and Steven G Self. Mapping HIV-1 Vaccine Induced T-Cell Responses: Bias Towards Less-Conserved Regions and Potential Impact on Vaccine Efficacy in the Step Study. PLoS One, 6(6):e20479, 2011. PubMed ID: 21695251. Show all entries for this paper.

Displaying record number 61952

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	Pol(973-)
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	AK9
Subtype	A3, B, C, CRF02_AG
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	Denmark, Guinea-Bissau
Experimental methods	HLA binding, Intracellular cytokine staining, Tetramer binding
Keywords	binding affinity, vaccine antigen design, non-susceptible form

Notes

95% and 100% of untreated, asymptomatic HIV-1-infected patients, from Guinea-Bissau and Denmark respectively, were able to subdominantly recognize 15 predicted CTL epitopes restricted by at least one of the 5 most common HLA supertypes, HLA-A*01, -A*02, -A*03, -B*07 and -B*44.
Epitope AK9, AIFQSSMTK, predicted and validated to be restricted by supertype A03, was found across geographic regions in 89% of HIV-1 sequences in Denmark clade-B and 40% Guinea-Bissau/Western Africa subtypes A3, C and CRF02_AG. Its equivalent peptide, Pol313 of the A03 pool did not elicit cytokine production, but bound the following HLA alleles moderately or well: A*3002, A*2902, A*3201 (A01 supertype); A*0301, A*1101, A*7401 (A03 supertype); A*3001 (A0103 supertype).

References

Karlsson2012 Ingrid Karlsson, Henrik Kløverpris, Kristoffer Jarlov Jensen, Anette Stryhn, Søren Buus, Annika Karlsson, Lasse Vinner, Philip Goulder, and Anders Fomsgaard. Identification of Conserved Subdominant HIV Type 1 CD8+ T Cell Epitopes Restricted within Common HLA Supertypes for Therapeutic HIV Type 1 Vaccines. AIDS Res. Hum. Retroviruses, 28(11):1434-1443, Nov 2012. PubMed ID: 22747336. Show all entries for this paper.

Displaying record number 62839

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HXB2 Location	Pol(313-321) RT(158-166) DNA(3021..3047)	Pol Epitope Map
Author Location	RT(158-166)
Epitope	`AIFQSSMTK`	Epitope Alignment
Epitope Name	AK9
Subtype	B, C
Species (MHC/HLA)	human
Immunogen	HIV-1 infection, engineered
Experimental methods	Other, Relative replication capacity assay
Keywords	acute/early infection, HLA associated polymorphism, chronic infection, protective allele

Notes

The in vitro replicative capacity (RC) of recombinant subtype B NL4-3 viruses expressing subtype C RT-integrase sequences derived from recently infected patients correlated positively with log subsequent VL set point and a higher rate of CD4 decline, while the RC of NL4-3 recombinants expressing subtype C RT-integrase sequences derived from chronically infected patients correlated positively with log VL but negatively with CD4 count. Protective & risk HLA alleles were associated with lower and higher RC values, respectively, and the number of HLA-associated polymorphisms in RT correlated positively with RC while the inverse was observed for integrase. About 90% of RT-integrase polymorphisms significantly associated with altered RC occurred inside or within 5 aa of A-list epitopes (LANL HIV Database).
RT polymorphism A158S and subtype C consensus A158 were associated with altered RC and are located within best-defined A-list epitope AIFQSSMTK, AK9, known to bind to A*03:01/A*11:01, as well as overlapping epitopes LPQGWKGSPA & SPAIFQSSM.
A158S occurred in 25 participant-derived recombinant viruses with a median RC of 0.88, while 453 analogous viruses with consensus A158 had a median RC of 0.92, relative to unmodified NL4-3.

References

Ojwach2018 Doty B. A. Ojwach, Daniel MacMillan, Tarylee Reddy, Vladimir Novitsky, Zabrina L. Brumme, Mark A. Brockman, Thumbi Ndung'u, and Jaclyn K. Mann. Pol-Driven Replicative Capacity Impacts Disease Progression in HIV-1 Subtype C Infection. J. Virol., 92(19), 1 Oct 2018. PubMed ID: 29997209. Show all entries for this paper.