Search CTL/CD8+ T-Cell Epitope Database

Found 14 matching records:

Displaying record number 59603

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HXB2 Location	Pol(90-98) Protease(34-42) DNA(2352..2378)	Pol Epitope Map
Author Location	Pol(90-98)
Epitope	`EEMNLPGRW`	Epitope Alignment
Epitope Name	EW9
Species (MHC/HLA)	human(A*68:02)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope, chronic infection

Notes

Correlation between HLA class I and spontaneous control of HIV-1 was significant for 7-8 epitopes when 341 chronic, HIV-infected subjects, divided into controllers and non-controllers, were tested for EliSpot responses to 257 optimally defined epitopes. 21 epitopes were associated with viral progression. Protective epitopes tend to cluster in regions of critical stability for the protein, therefore constraining escape.
EEMNLPGRW had a significantly positive association with HLA A*6802; it was recognized by 3/26 A*6802-positive subjects and 3/251 A*6802-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 54656

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HXB2 Location	Pol(90-98) Protease(34-42) DNA(2352..2378)	Pol Epitope Map
Author Location	Protease(34-42 HXB2)
Epitope	`EEMNLPGRW`	Epitope Alignment
		Show epitope variants
Epitope Name	EW9
Subtype	B
Species (MHC/HLA)	human(B18, B40, B44)
Immunogen	HIV-1 infection
Country	Germany
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	escape, variant cross-reactivity, mutation acquisition, HLA associated polymorphism, drug resistance

Notes

To assess HIV-1-specific CTL influence on development and patterns of drug resistance in protease (PR) 94 HLA-typed patients were analyzed. 10 new CTL epitopes were defined statistically and experimentally, and 26 correlations (positive and negative) between HLA class-I alleles and PR mutations - some leading to escape mutations - were detected, demonstrating that CTL epitopes can be predicted based on HLA-amino acid substitution associations.
Some patient CTL escape mutations were detectable by other CTLs of the same patient. Correlations between resistance mutations, polymorphisms and specific PR inhibitors were not detected.
HLA-B had the strongest impact on PR sequence change, though HLAs-A and -C also had some impact.
The authors suggest that CTL escape is active in developing drug-resistance related polymorphisms as well as major and minor mutations in HIV-1 infected persons.
HIV-1 subtype breakdown in this cohort was follows - 83/94 patients infected with subtype B virus, 3 with subtype C, 4 CRF01_AE, 1 CRF03_AB, 1 CRF15_01B and 2 subtype Ds.
This highly immunogenic index epitope, EEMNLPGRW, EW9, developed variants EEiNLPGRW, EW9 M/I, EEMdLPGRW, EW9 N/D, EdMNLPGRW, EW9 E/D, EdiNLPGRW, EW9 D/I, EEMNLPGkW, EW9 R/K, EEMNLsGRW, EW9 P/S. E35D and P39S mutants were located in the previously reported HLA-B44 restricted epitope EEMSLPGRW (EW9). The correlation between the minor drug mutation E35D and HLA-B44 was strong, while that of -B44 with P39S was weak. E35D mutations induced a strong decrease in CTL recognition, but few patient samples did mount specific responses against it giving a negative correlation between this mutation and HLA-B44. A novel association between the E35D mutant and HLA-B18 was also found.
Cross-reactivity of CTL recognition of EW9 and variants occurred for most patients. This showed that cells from several patients mount oligoclonal CTL responses, indicating immune system reactions to escape by recruitment of CTLs with new TCR specificities. On the other hand, most patients showed mutually exclusive recognition of variant epitopes containing either E35D or E35E; HLA-B44 subtypes and other factors tested could not explain this phenomenon.
EW9 epitope and variant peptides include the S37N substitution when compared to HXB2 strain sequences.
HLA-restrictions to this epitope were HLA-18, -40, -44.

References

Mueller2007 Sandra M. Mueller, Birgit Schaetz, Kathrin Eismann, Silke Bergmann, Michael Bauerle, Matthias Schmitt-Haendle, Hauke Walter, Barbara Schmidt, Klaus Korn, Heinrich Sticht, Bernd Spriewald, Ellen G. Harrer, and Thomas Harrer. Dual Selection Pressure by Drugs and HLA Class I-Restricted Immune Responses on Human Immunodeficiency Virus Type 1 Protease. J. Virol., 81(6):2887-2898, Mar 2007. PubMed ID: 17202219. Show all entries for this paper.

Displaying record number 59602

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HXB2 Location	Pol(90-98) Protease(34-42) DNA(2352..2378)	Pol Epitope Map
Author Location	Pol(90-98)
Epitope	`EEMNLPGRW`	Epitope Alignment
Epitope Name	EW9
Species (MHC/HLA)	human(B35:02, B35:03, B*53:01)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, optimal epitope, chronic infection

Notes

Correlation between HLA class I and spontaneous control of HIV-1 was significant for 7-8 epitopes when 341 chronic, HIV-infected subjects, divided into controllers and non-controllers, were tested for EliSpot responses to 257 optimally defined epitopes. 21 epitopes were associated with viral progression. Protective epitopes tend to cluster in regions of critical stability for the protein, therefore constraining escape.
EEMNLPGRW had a significantly positive association with HLA B*3502,B*3503,B*5301; it was recognized by 3/36 B*3502,B*3503,B*5301-positive subjects and 0/215 B*3502,B*3503,B*5301-negative subjects.

References

Displaying record number 59297

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HXB2 Location	Pol(90-98) Protease(34-42) DNA(2352..2378)	Pol Epitope Map
Author Location	Protease
Epitope	`EEMNLPGRW`	Epitope Alignment
Epitope Name	EW9
Species (MHC/HLA)	human(B*44)
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 epitope EEMNLPGRW was associated with delayed 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 59601

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HXB2 Location	Pol(90-98) Protease(34-42) DNA(2352..2378)	Pol Epitope Map
Author Location	Pol(90-98)
Epitope	`EEMNLPGRW`	Epitope Alignment
Epitope Name	EW9
Species (MHC/HLA)	human(B*44)
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.
EEMNLPGRW had a significantly positive association with HLA B*44; it was recognized by 28/64 B*44-positive subjects and 6/277 B*44-negative subjects.

References

Displaying record number 56384

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HXB2 Location	Pol(90-98) Protease(34-42) DNA(2352..2378)	Pol Epitope Map
Author Location	Protease(34-42)
Epitope	`EEMNLPGRW`	Epitope Alignment
Epitope Name	EW9
Subtype	B
Species (MHC/HLA)	human(B*44)
Immunogen	HIV-1 infection
Country	Australia, Canada, Germany, United States
Experimental methods
Keywords	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*44-associated substitutions within optimally defined epitope EEMNLPGRW are at positions E2 and N4, EeMnLPGRW.

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 52574

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HXB2 Location	Pol(90-98) Protease(34-42) DNA(2352..2378)	Pol Epitope Map
Author Location	Protease(34-42)
Epitope	`EEMNLPGRW`	Epitope Alignment
Species (MHC/HLA)	human(B44)
Immunogen
Experimental methods
Keywords	optimal epitope, A-list

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 53137

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HXB2 Location	Pol(90-98) Protease(34-42) DNA(2352..2378)	Pol Epitope Map
Author Location	Protease
Epitope	`EEMNLPGRW`	Epitope Alignment
Epitope Name	EW9
Species (MHC/HLA)	human(B44)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords	epitope processing, supervised treatment interruptions (STI), immunodominance

Notes

Protease and integrase are shown to be frequently targeted by CD8 T-cell responses (23% and 68% of 56 HIV+ patients, respectively). Responses tend to cluster in conserved regions of Int, although 1 high conserved region had no responses. CTL frequencies per unit protein length for Pro and Int were similar to other HIV non-structural proteins. Three novel HLA class I-restricted optimal epitopes were found and characterized with fine mapping.
The epitope includes residue M36, which is a known accessory mutation site in individuals treated with PIs.

References

Rodriguez2004 William R. Rodriguez, Marylyn M. Addo, Almas Rathod, Cecily A. Fitzpatrick, Xu G. Yu, Beth Perkins, Eric S. Rosenberg, Marcus Altfeld, and Bruce D. Walker. CD8+ T Lymphocyte Responses Target Functionally Important Regions of Protease and Integrase in HIV-1 Infected Subjects. J. Transl. Med., 2(1):15, 21 May 2004. PubMed ID: 15154967. Show all entries for this paper.

Displaying record number 58240

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HXB2 Location	Pol(90-98) Protease(34-42) DNA(2352..2378)	Pol Epitope Map
Author Location	Pol(90-98)
Epitope	`EEMNLPGRW`	Epitope Alignment
		Show epitope variants
Subtype	B
Species (MHC/HLA)	human(B*44:02)
Immunogen	HIV-1 infection
Patient MHC/HLA	MM33: A02:01, A68:01, B07:02, B44:02, C05:01, C07:02
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords	dynamics, escape, acute/early infection, autologous responses, characterizing CD8+ T cells

Notes

Multifunctionality of CTL against transmitted or founder HIV-1 isolates during early or acute infection was examined for correlation with escape mutation selection. The earliest CTL responses were oligofunctional, and progressively became more multifunctional. A significant association was found between total CTL response and order of escape selection, and between epitope entropy with the rate of emergence of escape mutants.
18-mer DTGADDTVLEEMNLPGRW (Pol 81-98) contains epitope EEMNLPGRW, that shows early evidence of escape or variation by 96 days from onset of symptoms (DFOSx). This epitope elicited CTL response in patient MM33.

References

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

Displaying record number 54289

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HXB2 Location	Pol(90-98) Protease(34-42) DNA(2352..2378)	Pol Epitope Map
Author Location	Pol(2361-)
Epitope	`EEMNLPGRW`	Epitope Alignment
Species (MHC/HLA)	human(B*44:02)
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 fourth position of the epitope EEMnLPGRW has a mutational pattern that is correlated the host carrying HLA B*4402.

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 58987

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HXB2 Location	Pol(90-98) Protease(34-42) DNA(2352..2378)	Pol Epitope Map
Author Location	Protease(34-42)
Epitope	`EEMNLPGRW`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*44:02)
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 EEMNLPGRW, whose variation at position 35 is associated with SNP rs2523577.

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 54400

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HXB2 Location	Pol(90-98) Protease(34-42) DNA(2352..2378)	Pol Epitope Map
Author Location	Pol(2355-)
Epitope	`EEMNLPGRW`	Epitope Alignment
Epitope Name	EW9
Species (MHC/HLA)	human(B*44:03)
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.
This HLA-B*4403 HIV mutation association was only picked up using statistics that incorporate the phylogeny. The second position, EeMNLPGRW, is the anchor residue association.

References

Displaying record number 60929

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HXB2 Location	Pol(90-98) Protease(34-42) DNA(2352..2378)	Pol Epitope Map
Author Location	Protease(34-42)
Epitope	`EEMNLPGRW`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*44:03)
Immunogen	HIV-1 infection
Patient MHC/HLA	11439: A01:01, A29:02, B38:01, B44:03, C12:03, C16:01; 94153: A25:01, A68:01, B14:02, B44:02, C05:01, C08:02
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	acute/early infection

Notes

The extent to which set-point viremia is affected by early HIV-infection T cell responses to either conserved or variable epitopes was studied. 23 ART-naive subjects were characterized for CTL responses for 6 months, postinfection. While most CTL responses (73/123) were targeted against variable HIV-1 epitopes, recognition of conserved epitopes (16/123) was associated with lower set point viremia. This was independent of HLA type and also functional avidity of the CTL response. Most of the conserved responses were targeted to Gag and Pol epitopes.
EEMNLPGRW, restricted by B*4403, was recognized by 2 patients with the restricting allele.

References

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

Displaying record number 56960

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HXB2 Location	Pol(90-98) Protease(34-42) DNA(2352..2378)	Pol Epitope Map
Author Location	Pol
Epitope	`EEMNLPGRW`	Epitope Alignment
Subtype	C, D
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.
EEMNLPGRW was a predicted epitope restricted by B44 supertype. 2/31 patient(s) responded to it; 1 of them was known to carry an allele of B44 supertype. Responding patients were infected with HIV clade(s) C, D.

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.