Search CTL/CD8+ T-Cell Epitope Database

Found 34 matching records:

Displaying record number 57518

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location
Epitope	`GPGHKARVL`	Epitope Alignment
Epitope Name	GL9
Species (MHC/HLA)	human(A*02:01)
Immunogen	in vitro stimulation or selection
Experimental methods	Tetramer binding
Keywords

Notes

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

References

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

Displaying record number 57528

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	p24(223-231)
Epitope	`GPGHKARVL`	Epitope Alignment
Epitope Name	G9VL
Species (MHC/HLA)	human, transgenic mouse(B*07)
Immunogen	HIV-1 infection, vaccine
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, HLA binding
Keywords	vaccine-induced immune responses, vaccine antigen design

Vaccine Details

Vaccine type	polyepitope
Vaccine strain	multiple epitope immunogen
Vaccine component	HIV-1

Notes

The study objective was to design a vaccine construct containing HIV-1 epitopes that would generate broad CD8+ responses. Among 14 known B7-restricted epitopes, 11 induced a response in B*07 transgenic mice. Among 11 novel candidate epitopes, all induced a response in B*07 mice, and all induced a response in at least 1 human B7+ donor. Immunological recognition of these epitopes was confirmed in HLA-B*0702 HIV-1-infected individuals.
GPGHKARVL is a known B07 epitope that was not recognized by B*07 transgenic mice.

References

Cardinaud2009 Sylvain Cardinaud, Romain Bouziat, Pierre-Simon Rohrlich, Sophie Tourdot, Laurence Weiss, Pierre Langlade-Demoyen, Anne Burgevin, Susana Fiorentino, Peter van Endert, and François A. Lemonnier. Design of a HIV-1-Derived HLA-B07.02-Restricted Polyepitope Construct. AIDS, 23(15):1945-1954, 24 Sep 2009. PubMed ID: 19644347. Show all entries for this paper.

Displaying record number 53107

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	p24(223-231)
Epitope	`GPGHKARVL`	Epitope Alignment
Species (MHC/HLA)	human(B*07)
Immunogen	HIV-1 infection
Country	Spain
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay, Proliferation
Keywords	HAART, ART, supervised treatment interruptions (STI)

Notes

Structured treatment interruption (STI) alone is not able to control viral replication in chronically infected patients, probably due to lack of strong, maintained T-helper cell responses. HIV-1 specific CD8+ T-cell responses were shown to increase significantly until the end of the follow up, but were not correlated with viral load.
4/7 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 58362

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	p24
Epitope	`GPGHKARVL`	Epitope Alignment
Epitope Name	B7 GL9
Subtype	B
Species (MHC/HLA)	human(B*07)
Immunogen	in vitro stimulation or selection, HIV-1 infection, vaccine
Country	South Africa, United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining, Tetramer binding
Keywords	vaccine antigen design

Vaccine Details

Vaccine type	adenovirus type 5 (Ad5)
Vaccine strain	B clade, C clade
Vaccine component	Gag

Notes

To increase coverage of functional epitopes across clades and to elicit cross-clade recognition, mosaic antigens comprising HIV Gag sequences from clades B and C were used to construct a bivalent mosaic vaccine. This was tested for recognition by Gag epitope-specific CTL, thereby comparing and confirming the processing, presentation and antigenicity of synthetic epitopes to natural ones. All 8 clade B epitopes tested in 12 US subjects as well as all 5 clade C epitopes tested in 10 South African subjects were expressed, stimulated CTL cytokine production and induced specific helper CD4 T cell responses. Mosaic-antigens however, elicited greater cross-clade recognition than natural antigens.
Epitope-GPGHKARVL-containing peptides, CQGVGGPGHKARVLAEAMS for Clade B and CQGVGGPSHKARVLAEAMS for Clade C were successfully used for detection of immune responses, but Clade C peptide could not stimulate clade B GL9-specific CTL.

References

Ndhlovu2011 Zaza M. Ndhlovu, Alicja Piechocka-Trocha, Seanna Vine, Ashley McMullen, Kegakilwe C. Koofhethile, Phillip J. R. Goulder, Thumbi Ndung'u, Dan H. Barouch, and Bruce D. Walker. Mosaic HIV-1 Gag Antigens Can Be Processed and Presented to Human HIV-Specific CD8+ T Cells. J. Immunol., 186(12):6914-6924, 15 Jun 2011. PubMed ID: 21576505. Show all entries for this paper.

Displaying record number 62121

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	p24(355-363 NL4-3)
Epitope	`GPGHKARVL`	Epitope Alignment
Species (MHC/HLA)	human(B*07)
Immunogen	computer prediction
Experimental methods	Other, Relative replication capacity assay
Keywords	vaccine antigen design, viral fitness and reversion

Notes

Computational models were used to translate published HIV-1 sequence data into quantitative viral fitness landscapes with peaks and valleys, that are a function of the amino acid sequences of its constituent proteins. In this case, Clade B Gag was modeled. Predictions were tested against in vitro fitness measurements and were consistent.
Epitope GPGHKARVL is used as an example where each amino acid position within the epitope is associated with a different energy cost, ΔE, and the greater the cost the higher the fitness penalty. Observed HLA-associated escape position at H357 is one of the positions (including V362) with the lowest h_i value, i.e. the least energetically costly to change. Positions G355 and P356 have an infinite energy cost within the model to mutate and so do not.
Based on fitness costs, the authors created a rank-ordered bar chart called the "Epitope Index" and marked out immunodominant response associations on it. The epitope index reads Gag: (164-172)-B*57; (162-172)-B*57 i.e. KF11; (167-175)-A*26; (260-267)-B*08; (240-249)-B*57 i.e. TW10; (296-306)-B*14; (147-155)-B*57; (349-359)-A*11; (263-272)-B*27; (269-277)-B*15; (145-155)-A*25; (306-316)-B*44, from highest to lowest fitness costs.
Brumme2009 is not annotated in this database as epitopes were not immunologically defined, but the table of polymorphisms is available at https://www.hiv.lanl.gov/content/immunology/pdf/2010/escape_article_supplement.html. and a review of the work is available on the main page, hiv.lanl.gov under 'Tools and Data Sets', "Identifying HLA-Associated Polymorphisms in HIV-1" (PDF).

References

Ferguson2013a Andrew L. Ferguson, Jaclyn K. Mann, Saleha Omarjee, Thumbi Ndung'u, Bruce D Walker, and Arup K. Chakraborty. Translating HIV Sequences into Quantitative Fitness Landscapes Predicts Viral Vulnerabilities for Rational Immunogen Design. Immunity, 38(3):606-617, 21 Mar 2013. PubMed ID: 23521886. Show all entries for this paper.

Displaying record number 56367

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	p24(355-363)
Epitope	`GPGHKARVL`	Epitope Alignment
Epitope Name	GL9
Subtype	B
Species (MHC/HLA)	human(B*07)
Immunogen	HIV-1 infection
Country	Australia, Canada, Germany, United States
Experimental methods
Keywords	escape, HLA associated polymorphism

Notes

98 newly infected patients were studied to track early host HLA and Gag/Pol/Nef epitope immune responses' association with viral evolution. Response hierarchies were the same as those for later infection, and 50% of the most rapidly substituting epitopes were restricted by protective HLA, e.g. Gag B*57-associated mutations which were the most rapidly reverting upon transmission to a non-B*57-host. While there are great differences in mutation rates and reversions across the HIV proteome, most early viral change is driven by immune pressure.
HLA-driven epitope evolution was seen in 80% of published CTL epitopes.
HLA-B*07-associated substitution within optimally defined epitope GPGHKARVL is at positions G3, GPgHKARVL. With a low recognition frequency of ~20%, GL9 also has a low rate of escape.

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 1783

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	p24(223-231)
Epitope	`GPGHKARVL`	Epitope Alignment
Species (MHC/HLA)	human(B*07)
Immunogen	HIV-1 infection
Experimental methods
Keywords	rate of progression, acute/early infection

Notes

The CTL response to optimally defined CTL epitopes restricted by HLA class I A and B alleles in individuals who coexpressed HLA A*02, A*03, and B*07 was studied in eight HIV-1-infected subjects, two with acute infection, five with chronic, and one long-term non-progressor (LTNP)
2 to 17 epitopes were recognized in a given individual, A*02-restricted CTL response tended to be narrow and never dominated the response, and 25/27 epitopes were targeted by at least one person.
Subjects with chronic HIV-1 infection recognized between 2-8 out of 11 B*07-restricted epitopes.
An acute seroconvertor homozygous for the B*07 allele recognized five B*07-restricted epitopes.
The other acute seroconvertor failed to recognize any of the 11 B*07-restricted epitopes tested.
The B*07-restricted CTL response was highly variable and there was no clearly dominant epitope.

References

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

Displaying record number 56337

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	Gag
Epitope	`GPGHKARVL`	Epitope Alignment
Subtype	B, C
Species (MHC/HLA)	human(B*07)
Immunogen	HIV-1 infection
Country	Canada, South Africa
Experimental methods
Keywords

Notes

A statistical model, the phylogenetic dependency network (PDN), was developed to differentiate the confounding effects of codon variation, linkage disequilibrium of HLA alleles and HIV phylogeny from HLA-associated evolution including HIV selection by HLA-pressure and codon evolution.
This approach was applied to 2 cohorts of 1144 Gag sequences from HIV-infected individuals, generating associations between HIV codons themselves and codons with HLA alleles. Results generated predicted escapes that confirmed that escape kinetics and compensating mutations are consistent across clades. General patterns of covariation and CTL adaptation were determined. Some clade-based differences were identified.
Clades B and C, HLA-B*07-restricted optimal epitope GPGHKARVL has a susceptible form, GPsHKARVL.

References

Carlson2008 Jonathan M. Carlson, Zabrina L. Brumme, Christine M. Rousseau, Chanson J. Brumme, Philippa Matthews, Carl Kadie, James I. Mullins, Bruce D. Walker, P. Richard Harrigan, Philip J. R. Goulder, and David Heckerman. Phylogenetic Dependency Networks: Inferring Patterns of CTL Escape and Codon Covariation in HIV-1 Gag. PLoS Comput Biol, 4(11):e1000225, Nov 2008. PubMed ID: 19023406. Show all entries for this paper.

Displaying record number 59731

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	Gag(355-363)
Epitope	`GPGHKARVL`	Epitope Alignment
Epitope Name	GL9
Species (MHC/HLA)	human(B*07)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope, 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.
GPGHKARVL had a significantly positive association with HLA B*07; it was recognized by 16/38 B*07-positive subjects and 2/303 B*07-negative subjects.

References

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

Displaying record number 61967

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	Gag(355-363)
Epitope	`GPGHKARVL`	Epitope Alignment
		Show epitope variants
Subtype	A, D
Species (MHC/HLA)	human(B*07:02)
Immunogen	HIV-1 infection
Patient MHC/HLA	1394: A02:01, A68:02, B07:02, B13:02, C04:01, C06:02; 2545: A30:02, A68:02, B07:02, B18:01, C07:02, C07:04; 2044: A03:08, A29:01, B07:02, B08:01, C07:02; 2035: A23:01, A30:01, B07:02, B15:10, C03:04, C07:14; 2320: A02:01, A33:01, B07:02, B49:01, C07:01, C07:02; 2644: A36:01, A68:02, B07:02, B53:01, C06:02, C17:01; 2423: A68:02, B07:02, C07:02; 2400: A02:01, A68:02, B07:02, B42:01, C08:02, C17:01; 2427: A29:02, A68:02, B07:02, B39:10, C07:27, C12:03
Country	Kenya
Experimental methods	CD8 T-cell Elispot - IFNγ, Other, Tetramer binding
Keywords	subtype comparisons, HIV exposed persistently seronegative (HEPS), assay or method development

Notes

A systematic analysis of clade A or D epitopes that bind either protective HLA-A*0101 or susceptible HLA-B*0702 using the iTopia epitope discovery system was conducted. Broad epitope and variant recognition, and immune response was seen with the susceptible HLA allele, while a focused recognition of multiple epitope subtypes was seen associated with the protective HLA allele.
Novel epitopes were discovered using the iTopia system (3 assays: peptide binding, binding affinity, and off-rate).
Four new amino acids at anchor positions P2 (Lys, Arg, Thr, Iso) and P9 (Lys, Thr, Arg, Gly) were identified for B*0702 binding, including polar basic residues K and R, showing that B*0702-restricted epitopes are more tolerant to amino acid changes than known previously.
Previously known B*0702-restricted Gag epitope GPGHKARVL and a known variant, GPsHKARVL, was recognized by seronegative subjects as well as HIV-1 patients and bound HLA-B*0702. 6/16 B*0702+ female subjects responded to the epitope, with a mean of 167 SFU/million cells.

References

Luo2012 Ma Luo, Christina A. Daniuk, Tamsir O. Diallo, Rupert E. Capina, Joshua Kimani, Charles Wachihi, Makubo Kimani, Thomas Bielawny, Trevor Peterson, Mark G. R. Mendoza, Sandra Kiazyk, T. Blake Ball, and Francis A. Plummer. For Protection from HIV-1 Infection, More Might Not Be Better: A Systematic Analysis of HIV Gag Epitopes of Two Alleles Associated with Different Outcomes of HIV-1 Infection. J. Virol., 86(2):1166-1180, Jan 2012. PubMed ID: 22072744. Show all entries for this paper.

Displaying record number 58864

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	Gag(355-363)
Epitope	`GPGHKARVL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*07:02)
Immunogen	HIV-1 infection
Country	Australia
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	escape, optimal epitope, HLA associated polymorphism

Notes

Epitopes that have undergone escape are often still immunogenic. Scanning for epitopes that encompass HLA-specific polymorphisms revealed 97 HLA-polymorphism associations in which the mutation resulted in the creation rather than abolition of an epitope, termed a "neo-epitope". This study examined 9 neo-epitopes that were well-characterized optimal epitopes that elicit T-cell responses in chronic infection. HIV-1 adaptation not only abrogates the immune recognition of early targeted epitopes, but may also increase immune recognition to other epitopes, which elicit immunodominant but non-protective T-cell responses.
Neo-epitope GPGHKARVL underwent adaptation from GPSHKARVL. 5 subjects had higher EliSpot responses to the neo-epitope than to the non-adapted form.
HLA-B*0702-expressing PBMCs from 2 individuals were cultured with GL9 adapted and non-adapted epitopes to generate epitope-specific T-cell lines. The frequencies of central memory and effector memory T cells were not significantly different whether directed against non-adapted or adapted epitopes.
No difference was found in TCR expression between epitope-specific CTLs from adapted and non-adapted forms of this epitope.

References

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

Displaying record number 58977

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	Gag(355-363)
Epitope	`GPGHKARVL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*07:02)
Immunogen	HIV-1 infection
Country	Australia, Canada, Spain, Switzerland
Experimental methods	Other
Keywords	mutation acquisition

Notes

Computational genome-wide scans were run to find associations between (subjects' ) host genome DNA polymorphisms, and infecting HIV-1 genome sequence variation from 1071 subjects, as well as their viral load (VL). Such genome-to-genome approaches also reveal sites of single nucleotide polymorphisms (SNPs) linked to variant HIV-1 amino acids that either limit viral efficiency or that are easily tolerated by it.
48 amino acid residues of HIV-1 were linked to human SNPs, and the variants were not antiretroviral drug resistance mutations. 50% of these viral amino acids were located within previously defined optimal epitopes, such as GPGHKARVL, whose variation at position 357 is associated with SNP rs2523612.

References

Bartha2013 István Bartha, Jonathan M. Carlson, Chanson J. Brumme, Paul J. McLaren, Zabrina L. Brumme, Mina John, David W. Haas, Javier Martinez-Picado, Judith Dalmau, Cecilio López-Galíndez, Concepción Casado, Andri Rauch, Huldrych F. Günthard, Enos Bernasconi, Pietro Vernazza, Thomas Klimkait, Sabine Yerly, Stephen J. O'Brien, Jennifer Listgarten, Nico Pfeifer, Christoph Lippert, Nicolo Fusi, Zoltán Kutalik, Todd M. Allen, Viktor Müller, P. Richard Harrigan, David Heckerman, Amalio Telenti, and Jacques Fellay. A Genome-to-Genome Analysis of Associations between Human Genetic Variation, HIV-1 Sequence Diversity, and Viral Control. eLife, 2:e01123, 2013. PubMed ID: 24171102. Show all entries for this paper.

Displaying record number 61791

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location
Epitope	`GPGHKARVL`	Epitope Alignment
Epitope Name	GL9
Subtype	B
Species (MHC/HLA)	human(B*07:02)
Immunogen	HIV-1 infection, vaccine
Country	Japan
Experimental methods	CD8 T-cell Elispot - IFNγ, CTL suppression of replication, Intracellular cytokine staining
Keywords	vaccine-induced immune responses, variant cross-reactivity

Notes

Specific T cells - from 120 ART-naive, infected Japanese subjects previously exposed to the tHIVconsvX vaccine - that have the ability to suppress HIV-1 replication were identified as recognizing 17 optimal Gag epitopes. 9/17 eptiopes were associated with lower pVL and higher CD4 count, of which 5 remain associated with positive clinical outcome in 221 HIV-1 infected subjects and cross-recognized major HIV-1 variants. 2/5 epitopes were novel. Candidate tHIVconsvX vaccine is composed of 6 conserved Gag and Pol regions.
B*0702-restricted epitope GPGHKARVL was found in 15-mer peptide pairs C107/108. 4 HLA-B*0702-carrying and 3 non-B*0702 responders to this epitope were detected by EliSpot out of 53 subjects.

References

Murakoshi2018 Hayato Murakoshi, Chengcheng Zou, Nozomi Kuse, Tomohiro Akahoshi, Takayuki Chikata, Hiroyuki Gatanaga, Shinichi Oka, Tomáš Hanke, and Masafumi Takiguchi. CD8+ T Cells Specific for Conserved, Cross-Reactive Gag Epitopes with Strong Ability to Suppress HIV-1 Replication. Retrovirology, 15(1):46, 3 Jul 2018. PubMed ID: 29970102. Show all entries for this paper.

Displaying record number 56478

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	p24
Epitope	`GPGHKARVL`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*07:02)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	HLA associated polymorphism

Notes

HLA-associated polymorphisms were studied in a cohort of 710 chronic subtype C patients from South Africa. 84 HLA Class I-associated polymorphisms were identified, 73% of them with HLA-B. The viral set points associated with HLA allele correlated with the number of reversions associated with that allele, (HLA-B in Gag, HLA-C in Pol).
GPGHKARVL is a previously described HLA-B*0702-restricted epitope (part of Gag reacting peptide MTACQGVGGPgHKARVL) that contains a B*0702-associated sequence polymorphism at residue G (GPgHKARVL).

References

Matthews2008 Philippa C. Matthews, Andrew Prendergast, Alasdair Leslie, Hayley Crawford, Rebecca Payne, Christine Rousseau, Morgane Rolland, Isobella Honeyborne, Jonathan Carlson, Carl Kadie, Christian Brander, Karen Bishop, Nonkululeko Mlotshwa, James I. Mullins, Hoosen Coovadia, Thumbi Ndung'u, Bruce D. Walker, David Heckerman, and Philip J. R. Goulder. Central Role of Reverting Mutations in HLA Associations with Human Immunodeficiency Virus Set Point. J. Virol., 82(17):8548-8559, Sep 2008. PubMed ID: 18596105. Show all entries for this paper.

Displaying record number 53930

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	( C consensus)
Epitope	`GPGHKARVL`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*07:02)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, optimal epitope

Notes

A comprehensive analysis of 160 class I T cell responses in 578 individuals from KwaZulu-Natal, South Africa was performed. Gag-specific responses were associated with lowering viremia, while Env, accessory and regulatory protein-specific responses were associated with higher viremia.
Mutational patterns in the G3 residue of GPGHKARVL are associated with the presence of the HLA presenting molecule in the host.

References

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

Displaying record number 54288

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	p24(1858-)
Epitope	`GPGHKARVL`	Epitope Alignment
Species (MHC/HLA)	human(B*07:02)
Immunogen	HIV-1 infection
Country	Australia
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	escape, HLA associated polymorphism

Notes

Host HLA associated mutational patterns in HIV can be a consequence of immune escape, but to cleanly resolve whether or not such patterns are the result of lineage effects or immune pressure, it is helpful to incorporate the phylogenetic history of the virus into the test statistics. Most of the HLA associations that appeared to result from immune escape in an earlier study (Moore et al., Science 296:1439 2002) were found to be a consequence of the phylogenetic history of the virus, not immune escape. Other HLA associations were validated, and some additional HLA-associated mutations were identified through incorporating the viral phylogenetic tree in the analysis.
The third position of this epitope GPgHKARVL has a mutational pattern that is correlated HLA B*0702. This epitope was experimentally tested using IFN-gamma Elispot and functional avidity studies.

References

Bhattacharya2007 Tanmoy Bhattacharya, Marcus Daniels, David Heckerman, Brian Foley, Nicole Frahm, Carl Kadie, Jonathan Carlson, Karina Yusim, Ben McMahon, Brian Gaschen, Simon Mallal, James I. Mullins, David C. Nickle, Joshua Herbeck, Christine Rousseau, Gerald H. Learn, Toshiyuki Miura, Christian Brander, Bruce Walker, and Bette Korber. Founder Effects in the Assessment of HIV Polymorphisms and HLA Allele Associations. Science, 315(5818):1583-1586, 16 Mar 2007. PubMed ID: 17363674. Show all entries for this paper.

Displaying record number 1258

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	p24(223-231 SF2)
Epitope	`GPGHKARVL`	Epitope Alignment
Epitope Name	GL9
Species (MHC/HLA)	human(B*07:02)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

HIV+ individual AC-06 was tested for reactive overlapping peptides spanning all HIV-1 proteins in an ELISPOT and was found to react with 12 peptides from 7 proteins, suggesting that the breadth of CTL responses are underestimated if accessory proteins are not included in the study.
The response to GPGHKARVL was dominant.

References

Altfeld2001c M. Altfeld, M. M. Addo, R. L. Eldridge, X. G. Yu, S. Thomas, A. Khatri, D. Strick, M. N. Phillips, G. B. Cohen, S. A. Islam, S. A. Kalams, C. Brander, P. J. Goulder, E. S. Rosenberg, B. D. Walker, and The HIV Study Collaboration.. Vpr is preferentially targeted by CTL during HIV-1 infection. J. Immunol., 167(5):2743-52, 1 Sep 2001. URL: http://www.jimmunol.org/cgi/content/full/167/5/2743. PubMed ID: 11509618. Show all entries for this paper.

Displaying record number 1213

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	( LAI)
Epitope	`GPGHKARVL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*07:02)
Immunogen
Experimental methods
Keywords	optimal epitope, A-list

Notes

C. Brander notes this is a B*0702 epitope.

References

GoulderPerCom2000 P. J. Goulder. personal communication. unpublished, 1999. Show all entries for this paper.

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 56599

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	p24(355-363)
Epitope	`GPGHKARVL`	Epitope Alignment
Epitope Name	GL9
Subtype	C
Species (MHC/HLA)	human(B*07:02, B5)
Immunogen	HIV-1 infection
Country	South Africa, Zambia
Experimental methods
Keywords	viral fitness and reversion, HLA associated polymorphism

Notes

A cohort of clade C-infected Zambian HIV-1 transmission pairs was studied. Accumulation in the donor of HLA-B restricted mutations in Gag, but not in Nef resulted in a reduced viral load in a recipient upon transmission.
20 mutations in Gag and 11 mutations in Nef, within or flanking CTL epitopes, were considered based on data from a Clade C South African cohort. HLA-B*0702- and B5-restricted GPGHKARVL (GL9) was associated with a polymorphism at GP(G)HKARVL.

References

Goepfert2008 Paul A. Goepfert, Wendy Lumm, Paul Farmer, Philippa Matthews, Andrew Prendergast, Jonathan M. Carlson, Cynthia A. Derdeyn, Jianming Tang, Richard A. Kaslow, Anju Bansal, Karina Yusim, David Heckerman, Joseph Mulenga, Susan Allen, Philip J. R. Goulder, and Eric Hunter. Transmission of HIV-1 Gag Immune Escape Mutations Is Associated with Reduced Viral Load in Linked Recipients. J. Exp. Med., 205(5):1009-1017, 12 May 2008. PubMed ID: 18426987. Show all entries for this paper.

Displaying record number 53692

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	p17
Epitope	`GPGHKARVL`	Epitope Alignment
Subtype	D
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 infection
Patient MHC/HLA	A23, A24, B35, B58, Cw4, Cw7
Country	Democratic Republic of the Congo
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	subtype comparisons, computational epitope prediction

Notes

Cross-clade CTL responses in 10 non-B HIV-1 infected individuals were evaluated. T-cell reactivity was tested against peptide pools of clade B Gag, Pol, Nef, Rev and Tat. Nine individuals demonstrated cross-reactive T-cell responses to clade A, B, and C Gag pools; 6/7 patients that responded to Nef-B also reacted to clade A and C Nef pools. An inverse correlation was observed between the sequence divergence of the HLA class I restricted epitopes and the height of the T-cell responses, which in Gag could be explained through variations in the HLA-anchor residues. 42% of the responses were directed to regions containing new epitopes.
Predicted epitope based on an HLA motif embedded in a reactive peptide from a person carrying a D clade Gag.

References

Geels2005 Mark J. Geels, Sheri A. Dubey, Kiersten Anderson, Elly Baan, Margreet Bakker, Georgios Pollakis, William A. Paxton, John W. Shiver, and Jaap Goudsmit. Broad Cross-Clade T-Cell Responses to Gag in Individuals Infected with Human Immunodeficiency Virus Type 1 Non-B Clades (A to G): Importance of HLA Anchor Residue Conservation. J. Virol., 79(17):11247-11258, Sep 2005. PubMed ID: 16103177. Show all entries for this paper.

Displaying record number 57209

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	Gag
Epitope	`GPGHKARVL`	Epitope Alignment
Species (MHC/HLA)	(B42)
Immunogen	HIV-1 infection
Country	Kenya
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	mother-to-infant transmission

Notes

HIV-1 peptide-specific IFN-γ responses were measured over the first year of life for vertically-infected infants. Late-infected infants (between months 1 and 12) had responses that were more rapid and more focused than those infected before 1 month of life.
2/5 infants tested recognized GPGHKARVL.

References

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

Displaying record number 362

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	p24(355-363 LAI)
Epitope	`GPGHKARVL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Patient MHC/HLA	003: A02, A03, B07, B51; 023: A02, A03, B07, B51
Experimental methods
Keywords	review, escape

Notes

HLA-identical sibling hemophiliac brothers were both infected with the same batch of factor VIII.
One, Patient 023, had a strong response to this peptide, the other, Patient 003, a weak response. They were tested 6-8 years after infection.
Goulder1997e is a review of immune escape that summarizes this study.

References

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

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

Displaying record number 1544

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	p24(223-231 SF2)
Epitope	`GPGHKARVL`	Epitope Alignment
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART, acute/early infection

Notes

Therapy provided during acute infection resulted in a narrower CTL response, stronger T help response, and a less diverse viral population than was seen in individuals treated during chronic infection.
The breadth and specificity of the response was determined using ELISPOT by studying 19 individuals with pre-seroconversion therapy (Group 1), 11 individuals with primary infection but post-seroconversion therapy (Group 2), and 10 individuals who responded to HAART given during chronic infection (Group 3), using 259 overlapping peptides spanning p17, p24, RT, gp41, gp120 and Nef.
Previously described and newly defined optimal epitopes were tested for CTL response.
Number of HLA-B7+ individuals that had a CTL response to this epitope broken down by group: 1/4 group 1, 2/3 group 2, and 0/1 group 3.

References

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

Displaying record number 52159

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	p24(223-231)
Epitope	`GPGHKARVL`	Epitope Alignment
Epitope Name	B7-GL9
Subtype	B
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Patient MHC/HLA	A3, B7, Cw7
Experimental methods
Keywords	dynamics, supervised treatment interruptions (STI), immunodominance, 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.
Only two epitopes were detected during acute infection in patient AC-06, B7 restricted gp41 epitope IPRRIRQGL and Gag GPGHKARVL. GPGHKARVL was the first targeted peptide, and remained immunodominant through the 34 month study period.
3/11 HLA-B7 individuals had detectable B7-restricted responses to this epitope during acute infection -- 10/15 of HLA-B7 epitopes tested were targeted by at least one person during acute infection. 1/4 individuals had detectable responses to this epitope after STI.

References

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

Displaying record number 52819

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	p24(223-231)
Epitope	`GPGHKARVL`	Epitope Alignment
Epitope Name	B7-GL9 Gag
Subtype	B
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	supervised treatment interruptions (STI), immunodominance, 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.
In the earliest sample at day18 the sequence for this epitope was gpShkarvl. gpghkarvl dominated at day 606; both were equally well recognized.
This was an immunodominant epitope, and was present in both viruses, the original strain and the superinfecting strain.

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 52831

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	p24(223-231)
Epitope	`GPGHKARVL`	Epitope Alignment
Epitope Name	B7-GL9 Gag
Subtype	B
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	supervised treatment interruptions (STI), immunodominance, 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.
In the earliest sample at day18 the sequence for this epitope was gpShkarvl. gpghkarvl dominated at day 606; both were equally well recognized.
This was an immunodominant epitope, and was present in both viruses, the original strain and the superinfecting strain.

References

Displaying record number 53369

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	( B consensus)
Epitope	`GPGHKARVL`	Epitope Alignment
Epitope Name	GL9
Subtype	B
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Patient MHC/HLA	A3, B7, Cw7
Country	United States
Experimental methods	Chromium-release assay, Cytokine production, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords	assay or method development, memory cells, characterizing CD8+ T cells

Notes

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

References

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

Displaying record number 53547

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	Gag(355-363)
Epitope	`GPGHKARVL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Patient MHC/HLA	A1, A3, B57, B7, Cw6, Cw7
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 54294

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	p24
Epitope	`GPGHKARVL`	Epitope Alignment
Epitope Name	B7-GL9(p24)
Species (MHC/HLA)	human(B7)
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 54764

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	Gag
Epitope	`GPGHKARVL`	Epitope Alignment
Epitope Name	B7-GL9 Gag (353-363)
Subtype	B
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Patient MHC/HLA	A1, A24, B27, B7
Country	France
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	binding affinity, immunodominance, characterizing CD8+ T cells

Notes

Since it is suggested that a single response to B27-KK10 epitope may be responsible for the association of HLA-B*2705 patients with AIDS-free survival, B27-KK10-specific CTLs were compared to other HLA-specific CTLs in phenotype, function, clonal diversity, and antigen sensitivity in 47 treatment-naive infected slow or nonprogressing patients.
cVL, the cell-associated viral load (number of infected cells harboring HIV DNA) correlated inversely with Gag-specific CTLs. This was most significant in HLA-B27 donors, and KK10 was identified as the peptide generating strongest CTL responses.
GPGHKARVL was a dominant epitope found in non-B27-KK10 CTL responses. TCR sequences were studied in 6 patients.

References

Almeida2007 Jorge R. Almeida, David A. Price, Laura Papagno, Zaïna Aït Arkoub, Delphine Sauce, Ethan Bornstein, Tedi E. Asher, Assia Samri, Aurélie Schnuriger, Ioannis Theodorou, Dominique Costagliola, Christine Rouzioux, Henri Agut, Anne-Geneviève Marcelin, Daniel Douek, Brigitte Autran, and Victor Appay. Superior Control of HIV-1 Replication by CD8+ T Cells Is Reflected by their Avidity, Polyfunctionality, and Clonal Turnover. J. Exp. Med., 204(10):2473-2485, 1 Oct 2007. PubMed ID: 17893201. Show all entries for this paper.

Displaying record number 55199

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location
Epitope	`GPGHKARVL`	Epitope Alignment
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	supertype, HLA cross-presentation

Notes

100 HIV-infected subjects were tested for response to optimally-defined CTL epitopes regardless of the subject's HLA type. Half of all detected responses were seen in the absence of the originally reported restricting HLA class I allele, and only 3% of epitopes were recognized exclusively in the presence of their original allele. Statistical and experimental methods were used to define additional HLA alleles associated with the epitopes.
In addition to its known HLA association (B07), an additional HLA (B40) was statistically predicted to be associated with this epitope.

References

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

Displaying record number 55706

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	Gag
Epitope	`GPGHKARVL`	Epitope Alignment
Subtype	B, F
Species (MHC/HLA)	human(B7)
Immunogen	HIV-1 infection
Country	Argentina
Experimental methods
Keywords	dynamics, escape

Notes

Dynamics of CTL escape mutations was studied theoretically by analyzing plasma samples from 302 subjects (collected over 20 years). HLA associated polymorphisms accumulated in a subtype-specific manner.
Epitope GPGHKARVL with anchor residues at G(P)GHKARV(L) mutates to GPsHKARVL which is moderately supported as escape by phylogenetic correction.

References

Dilernia2008 Dario Alberto Dilernia, Leandro Jones, Sabrina Rodriguez, Gabriela Turk, Andrea E Rubio, Sandra Pampuro, Manuel Gomez-Carrillo, Christian Bautista, Gabriel Deluchi, Jorge Benetucci, María Beatriz Lasala, Leonardo Lourtau, Marcelo Horacio Losso, Héctor Perez, Pedro Cahn, and Horacio Salomón. HLA-Driven Convergence of HIV-1 Viral Subtypes B and F Toward the Adaptation to Immune Responses in Human Populations. PLoS ONE, 3(10):e3429, 2008. PubMed ID: 18941505. Show all entries for this paper.

Displaying record number 54197

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HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	Gag(355-363)
Epitope	`GPGHKARVL`	Epitope Alignment
Epitope Name	GL9
Subtype	C
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, Other, Tetramer binding
Keywords	supertype, HLA cross-presentation, TCR usage, HLA associated polymorphism

Notes

14 promiscuous HIV-specific CTL epitopes presented by B7 supertype alleles were described. It was shown that CTLs targeting an identical epitope that are restricted by closely related but different HLA alelles differ in several ways: by occurrence of distinct HLA-specific escape mutations, by recruitment of distinct TCRs by peptide/MHC complexes, and by functional avidity of CTLs. Since there were no differences in the frequency, magnitude or immunodominance of the CTL responses restricted by different HLA alleles, it is suggested that the unique peptide/MHC complexes generated by closely related HLA induce qualitatively different CTL responses.
A strong negative association between B*0702 and conservation of sequence is observed.
Statistically significant associations between numbers of HLA-B0702 and -B4201 expressing subjects and epitope GPGHKARVL were found.

References

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

Displaying record number 62827

Download this epitope record as JSON.

HXB2 Location	Gag(355-363) p24(223-231) DNA(1852..1878)	Gag Epitope Map
Author Location	p24(355-363)
Epitope	`GPGHKARVL`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human
Immunogen	engineered
Experimental methods	Other, Relative replication capacity assay
Keywords	assay or method development, protective allele

Notes

NL4-3 Gag polyprotein random mutagenesis, high-throughput fitness profiling and in silico prediction of MHC-peptide binding affinity revealed that mutations in CTL epitopes presented by protective MHC-I alleles, vs. non-protective alleles, showed greater loss of experimental replicative capacity and lower levels of predicted reduction in MHC-I binding affinity. Together, these two variables could predict protectiveness of MHC-I alleles in a linear regression model. Analyses of intraperson viral evolution in 4 LTNP vs. 4 paired progressor subjects further supported paper conclusions.
After mutagenesis and passaging through human T cells, 64 single nucleotide mutations were observed in epitope GPGHKARVL (known to bind to B0702) with a log transformation of mean fitness score, relative to NL4-3, of -0.5781.

References

Du2017 Yushen Du, Tian-Hao Zhang, Lei Dai, Xiaojuan Zheng, Aleksandr M. Gorin, John Oishi, Ting-Ting Wu, Janice M. Yoshizawa, Xinmin Li, Otto O. Yang, Otoniel Martinez-Maza, Roger Detels, and Ren Sun. Effects of Mutations on Replicative Fitness and Major Histocompatibility Complex Class I Binding Affinity Are Among the Determinants Underlying Cytotoxic-T-Lymphocyte Escape of HIV-1 Gag Epitopes. mBio, 8(6), 28 Nov 2017. PubMed ID: 29184023. Show all entries for this paper.