Search CTL/CD8+ T-Cell Epitope Database

Found 15 matching records:

Displaying record number 59140

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HXB2 Location	Pol(838-847) Integrase(123-132) DNA(4596..4625)	Pol Epitope Map
Author Location	Integrase
Epitope	`STTVKAACWW`	Epitope Alignment
		Show epitope variants
Epitope Name	SW10
Subtype	B
Species (MHC/HLA)	human(B*57)
Immunogen	HIV-1 infection
Country	Germany
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	elite controllers

Notes

In a follow-up on the anonymous 1999 Berlin patient (not Timothy Brown of 2008), viral replication suppression was seen after 15 years of absence of ART. Half the HIV-specific CTL responses in this patient were restricted by HLA-B*57, with the most immunodominant being against Nef HW9, HTQGYFPDW.
B*57-restricted Integrase SW10, STTVKAACWW, elicited a very low CTL response when tested by EliSpot. Patient autologous sequence was SaTVKAACWW.

References

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

Displaying record number 60282

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HXB2 Location	Pol(838-847) Integrase(123-132) DNA(4596..4625)	Pol Epitope Map
Author Location	Pol(838-847)
Epitope	`STTVKAACWW`	Epitope Alignment
Epitope Name	SW10
Species (MHC/HLA)	human(B*57)
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.
STTVKAACWW had a significantly positive association with HLA B*57; it was recognized by 42/104 B*57-positive subjects and 7/237 B*57-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 54392

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HXB2 Location	Pol(838-847) Integrase(123-132) DNA(4596..4625)	Pol Epitope Map
Author Location	Integrase
Epitope	`STTVKAACWW`	Epitope Alignment
Epitope Name	B57-SW10(Int)
Species (MHC/HLA)	human(B57)
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 61010

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HXB2 Location	Pol(838-847) Integrase(123-132) DNA(4596..4625)	Pol Epitope Map
Author Location	Integrase(123-132)
Epitope	`STTVKAACWW`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
Patient MHC/HLA	21746: A01:01, A68:01, B40:01, B57:01, C03:04, C06:02, DQB103:02, DQB103:03
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.
STTVKAACWW, restricted by B57, was recognized by 1 patient 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 53139

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HXB2 Location	Pol(838-847) Integrase(123-132) DNA(4596..4625)	Pol Epitope Map
Author Location	Integrase
Epitope	`STTVKAACWW`	Epitope Alignment
Epitope Name	SW10
Species (MHC/HLA)	human(B57)
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), rate of progression, 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.
All 5 HLA-B57 patients recognized this epitope and were long-term nonprogressors.

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 52596

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HXB2 Location	Pol(838-847) Integrase(123-132) DNA(4596..4625)	Pol Epitope Map
Author Location	Integrase(123-132)
Epitope	`STTVKAACWW`	Epitope Alignment
Species (MHC/HLA)	human(B57)
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 53490

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HXB2 Location	Pol(838-847) Integrase(123-132) DNA(4596..4625)	Pol Epitope Map
Author Location	Pol
Epitope	`STTVKAACWW`	Epitope Alignment
Epitope Name	SW10
Subtype	B
Species (MHC/HLA)	human(B57)
Immunogen	HIV-1 infection
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.
Two escape mutations, at positions 2 and 3, were found in the most polymorphic residue in the epitope. These were shared between clades B and C. The T840N mutation at residue 2, sNtvkaacww, was significantly more common in persons expressing HLA-B57, often in conjunction with T841A or V sT[A/V]kaacww.

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 53651

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HXB2 Location	Pol(838-847) Integrase(123-132) DNA(4596..4625)	Pol Epitope Map
Author Location
Epitope	`STTVKAACWW`	Epitope Alignment
Species (MHC/HLA)	human(B*58:01, B57)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay
Keywords	responses in children, mother-to-infant transmission, characterizing CD8+ T cells

Notes

Escape mutations in TW10 and other B57-restricted epitopes were shown to arise early in infants following perinatal infection. Some escape variants were likely to have been transmitted vertically, from HLA-B57/5801 positive HIV-1 infected mothers, while others arose during infancy in cases where the children inherited the B57/5801 allele paternally. In contrast to adults, the majority of children showed a robust response to the escape variants, suggesting that infants are able to mount functional immune responses and drive immune escape and that a developing immune system may exhibit greater plasticity in recognizing viral variants.

References

Feeney2005a Margaret E. Feeney, Yanhua Tang, Katja Pfafferott, Kathleen A. Roosevelt, Rika Draenert, Alicja Trocha, Xu G. Yu, Cori Verrill, Todd Allen, Corey Moore, Simon Mallal, Sandra Burchett, Kenneth McIntosh, Stephen I. Pelton, M. Anne St. John, Rohan Hazra, Paul Klenerman, Marcus Altfeld, Bruce D. Walker, and Philip J. R. Goulder. HIV-1 Viral Escape in Infancy Followed by Emergence of a Variant-Specific CTL Response. J. Immunol., 174(12):7524-7530, 15 Jun 2005. PubMed ID: 15944251. Show all entries for this paper.

Displaying record number 58979

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HXB2 Location	Pol(838-847) Integrase(123-132) DNA(4596..4625)	Pol Epitope Map
Author Location	Integrase(123-132)
Epitope	`STTVKAACWW`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*57:01)
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 STTVKAACWW, whose variation at position 124 is associated with SNP chr6:31345421.

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 57955

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HXB2 Location	Pol(838-847) Integrase(123-132) DNA(4596..4625)	Pol Epitope Map
Author Location	Integrase(128-132)
Epitope	`STTVKAACWW`	Epitope Alignment
		Show epitope variants
Epitope Name	SW10
Subtype	B
Species (MHC/HLA)	human(B*57:01)
Immunogen	HIV-1 infection
Country	Australia
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	escape, 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 elicited T-cell responses in chronic infection.
STTVKAACWW underwent classical escape, with adapted forms STaVKAACWW and SnTVKAACWW having abrogated EliSpot responses.

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 60283

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HXB2 Location	Pol(838-847) Integrase(123-132) DNA(4596..4625)	Pol Epitope Map
Author Location	Pol(838-847)
Epitope	`STTVKAACWW`	Epitope Alignment
Epitope Name	SW10
Species (MHC/HLA)	human(B*58:01)
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.
STTVKAACWW had a significantly positive association with HLA B*5801; it was recognized by 2/9 B*5801-positive subjects and 5/228 B*5801-negative subjects.

References

Displaying record number 57205

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HXB2 Location	Pol(838-847) Integrase(123-132) DNA(4596..4625)	Pol Epitope Map
Author Location	Integrase(123-132)
Epitope	`STTVKAACWW`	Epitope Alignment
Epitope Name	SW9
Subtype	B
Species (MHC/HLA)	human(B*58:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	A30:01:01, A68:01:01, B58:01, B58:02
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	escape, acute/early infection, mutation acquisition, elite controllers

Notes

Full genome and longitudinal sequence analyses were performed on a transmission pair from transmission on, to determine the extent of B*5801-restricted epitope mutations as compared to other HIV-1 epitope variations. Although escape was rapid in HLA-B*5801-restricted epitopes in 3 proteins, relative control of viral replication was maintained. The protective effect of HLA allele B*5801 superseded the presence of rapid disease progression-associated HLA allele B*5802.
Integrase epitope STTVKAACWW escaped to SamVKAACWW (T125M) by day 137. Another variant seen was SaTVKAACWW. CTL response to the peptide GSNFTSTTVKAACWW (Gag 118-132), containing epitope SW10 was seen by day 221.

References

OConnell2009 Karen A. O'Connell, Jie Xu, Anna P. Durbin, Linda G. Apuzzo, Hejab Imteyaz, Thomas M. Williams, Stuart C. Ray, Joseph B. Margolick, Robert F. Siliciano, and Joel N. Blankson. HIV-1 Evolution Following Transmission to an HLA-B*5801-Positive Patient. J. Infect. Dis., 200(12):1820-1824, 15 Dec 2009. PubMed ID: 19909081. Show all entries for this paper.

Displaying record number 60284

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HXB2 Location	Pol(838-847) Integrase(123-132) DNA(4596..4625)	Pol Epitope Map
Author Location	Pol(838-847)
Epitope	`STTVKAACWW`	Epitope Alignment
Epitope Name	SW10
Species (MHC/HLA)	human(C*12)
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.
STTVKAACWW had a significantly positive association with HLA C*12; it was recognized by 3/37 C*12-positive subjects and 2/191 C*12-negative subjects.

References

Displaying record number 62851

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HXB2 Location	Pol(838-847) Integrase(123-132) DNA(4596..4625)	Pol Epitope Map
Author Location	Integrase(123-132)
Epitope	`STTVKAACWW`	Epitope Alignment
Epitope Name	SW10
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).
Polymorphism S119T and subtype C consensus S119 were associated with altered RC and are located 4 aa upstream from integrase best-defined A-list epitope STTVKAACWW (SW10), known to bind to B*57.
S119T occurred in 33 participant-derived recombinant viruses with a median RC of 0.95, while 403 analogous viruses with consensus S119 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.

Displaying record number 62894

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HXB2 Location	Pol(838-847) Integrase(123-132)	Pol Epitope Map
Author Location	Integrase(123-132)
Epitope	`STTVKAACWW`	Epitope Alignment
		Show epitope variants
Epitope Name	SW10
Subtype	B, C
Species (MHC/HLA)	human
Immunogen	HIV-1 infection, engineered
Experimental methods	Other, Relative replication capacity assay
Keywords	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 consensus 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 unmodified NL4-3, the introduction of integrase mutations S119T, S119P or Q136K did not mediate a significant reduction in RC while the introduction of S119R did not produce detectable cultured virus.
Relative to NL4-3 recombinant virus encoding wild-type SK-278 RT-integrase, the introduction of mutations S119T or S119R did not mediate a significant reduction in RC while the introduction of S119P did not produce detectable cultured virus, suggesting subtype-specific functional consequences of S119P/R mutants.
Residue 119 is located 4 AA upstream from best-defined integrase epitope STTVKAACWW (SW10, known to bind to B*57, but SaaVKAACWW in SK-278). Residue 119 is also located in epitope HTDNGSNF.

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.