Search CTL/CD8+ T-Cell Epitope Database

Found 24 matching records:

Displaying record number 60353

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HXB2 Location	Pol(262-270) RT(107-115) DNA(2868..2894)	Pol Epitope Map
Author Location	Pol(262-270)
Epitope	`TVLDVGDAY`	Epitope Alignment
Epitope Name	TY9
Species (MHC/HLA)	human(B*15:02)
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.
TVLDVGDAY had a significantly positive association with HLA B*1502; it was recognized by 1/1 B*1502-positive subjects and 3/303 B*1502-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 57718

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HXB2 Location	Pol(262-270) RT(107-115) DNA(2868..2894)	Pol Epitope Map
Author Location	Pol
Epitope	`TVLDVGDAY`	Epitope Alignment
		Show epitope variants
Epitope Name	TY9
Subtype	B
Species (MHC/HLA)	human(B*35)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression

Notes

Even though HLA-B*35-Px is associated with rapid disease progression to AIDS but HLA-B*35-Py is not, there was no difference in their association with CTL response to consensus epitopes in 16 subjects followed longitudinally during early HIV-1 infection. Surprisingly, HLA-B*35-Px rapid progressors responded to epitope-variants in spite of a lack of response to the consensus epitope; and the absence of any variant virus in the subject.
Consensus epitope TY9, TVLDVGDAY, was able to elicit CTL response in both HLA-B*35-Px and HLA-B*35-Py subjects, i.e. all 16 subjects.

References

Willberg2010 Christian B. Willberg, Keith E. Garrison, R. Brad Jones, Duncan J. Meiklejohn, Gerald Spotts, Teri J. Liegler, Mario A. Ostrowski, Annika C. Karlsson, Frederick M. Hecht, and Douglas F. Nixon. Rapid Progressing Allele HLA-B35 Px Restricted Anti-HIV-1 CD8+ T Cells Recognize Vestigial CTL Epitopes. PLoS One, 5(4):e10249, 2010. PubMed ID: 20422053. Show all entries for this paper.

Displaying record number 57612

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HXB2 Location	Pol(262-270) RT(107-115) DNA(2868..2894)	Pol Epitope Map
Author Location
Epitope	`TVLDVGDAY`	Epitope Alignment
Epitope Name	TY9
Subtype	B
Species (MHC/HLA)	(B*35)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	Flow cytometric T-cell cytokine assay, Intracellular cytokine staining, Proliferation
Keywords	acute/early infection

Notes

The study examined which CD8+ T cells are able to control viremia in early infection. Only a subset of patients in primary infection had CD4-independent CD8 proliferation. The remainder lacked HIV-1-specific CD8 T cells with proliferative capacity.
This epitope was used to examine CD8 T cells for proliferative capacity in patients identified and administered antiretroviral therapy within 4 months of seroconversion.

References

Heath2011 Sonya L. Heath, Steffanie Sabbaj, Anju Bansal, J Michael Kilby, and Paul A. Goepfert. CD8 T-Cell Proliferative Capacity Is Compromised in Primary HIV-1 Infection. J. Acquir. Immune Defic. Syndr., 56(3):213-221, Mar 2011. PubMed ID: 21079516. Show all entries for this paper.

Displaying record number 1998

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HXB2 Location	Pol(262-270) RT(107-115) DNA(2868..2894)	Pol Epitope Map
Author Location	RT
Epitope	`TVLDVGDAY`	Epitope Alignment
Epitope Name	Pol-TY9; RT-TY9
Subtype	B
Species (MHC/HLA)	human(B*35)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	HAART, ART

Notes

Among HIV+ individuals who carried HLA B*35, 8/21 (38%) recognized this epitope.

References

Sabbaj2003 Steffanie Sabbaj, Anju Bansal, G. Douglas Ritter, Christopher Perkins, Bradley H. Edwards, Ethan Gough, Jianming Tang, James J. Szinger, Bette Korber, Craig M. Wilson, Richard A. Kaslow, Mark J. Mulligan, and Paul A. Goepfert. Cross-Reactive CD8+ T Cell Epitopes Identified in US Adolescent Minorities. J. Acquir. Immune Defic. Syndr., 33(4):426-438, 1 Aug 2003. PubMed ID: 12869831. Show all entries for this paper.

Displaying record number 52253

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HXB2 Location	Pol(262-270) RT(107-115) DNA(2868..2894)	Pol Epitope Map
Author Location	Pol
Epitope	`TVLDVGDAY`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 infection
Patient MHC/HLA	A11, A3, B35, B51
Experimental methods
Keywords	mother-to-infant transmission

Notes

IFNgamma T-cell responses in breast milk of 5 HIV-1 infected women from the US and 6 from Zambia were tested with using Elispot. 11/11 women responded to Gag, 8/11 responded to Pol, 7/11 women to Nef, and 2/5 women to Env peptide pools. These responses were shown to be primarily due to CD8+ T-cells in one woman, and another woman had cytolytic responses measured by Cr-release.
T-cells in breast milk from a volunteer who was HLA A3, A11, B35, B51 induced IFNgamma after stimulation with either of two overlapping peptides that carry known B35 epitope TVLDVGDAY.
The frequencies of responses in the two compartments differed, and 2/4 women that responded to epitopes in Nef 101-205 and Pol 601-710 showed responses in breast milk but no detectable responses in peripheral blood cells.

References

Sabbaj2002a Steffanie Sabbaj, Bradley H. Edwards, Mrinal K. Ghosh, Katherine Semrau, Sanford Cheelo, Donald M. Thea, Louise Kuhn, G. Douglas Ritter, Mark J. Mulligan, Paul A. Goepfert, and Grace M. Aldrovandi. Human Immunodeficiency Virus-Specific CD8(+) T Cells in Human Breast Milk. J. Virol., 76(15):7365-7373, Aug 2002. PubMed ID: 12097549. Show all entries for this paper.

Displaying record number 53053

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HXB2 Location	Pol(262-270) RT(107-115) DNA(2868..2894)	Pol Epitope Map
Author Location	RT(107-115)
Epitope	`TVLDVGDAY`	Epitope Alignment
		Show epitope variants
Subtype	B
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 infection
Country	Canada
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay
Keywords	HAART, ART, immunotherapy, variant cross-reactivity

Notes

Accumulation of specific antiretroviral drug-resistance mutations in Pol gene was shown to sustain and even enhance the antigenicity and immunogenicity of HIV-1 CTL epitopes in this region. Several different patterns of cross-reactivity and selective recognition of wild-type and variant epitopes were found.
TiLDVGDAY, TVLDVGDAf and TiLDVGDAf variants are detected due to appearance of V108I and Y115F resistance mutations. Complete cross-reactivity of wild-type and variant peptides was observed.

References

Mason2004 Rosemarie D. Mason, M. Ian Bowmer, Constance M. Howley, Maureen Gallant, Jennifer C. E. Myers, and Michael D. Grant. Antiretroviral Drug Resistance Mutations Sustain or Enhance CTL Recognition of Common HIV-1 Pol Epitopes. J. Immunol., 172(11):7212-7219, 1 Jun 2004. PubMed ID: 15153547. Show all entries for this paper.

Displaying record number 54359

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HXB2 Location	Pol(262-270) RT(107-115) DNA(2868..2894)	Pol Epitope Map
Author Location	RT
Epitope	`TVLDVGDAY`	Epitope Alignment
Epitope Name	B35-TY9(RT)
Species (MHC/HLA)	human(B35)
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 56014

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HXB2 Location	Pol(262-270) RT(107-115) DNA(2868..2894)	Pol Epitope Map
Author Location	RT
Epitope	`TVLDVGDAY`	Epitope Alignment
Epitope Name	TY9(RT)
Subtype	B
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 infection
Country	China
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	chronic infection

Notes

49 ART-naive chronically HIV-1 infected Chinese subjects' CTLs were tested with 413 OLPs in IFN-γ assays, determining optimal epitopes specific for Chinese Clade B HIV-1 sequences.
An inverse correlation was found between CTL response and viral load.
Targeted peptides have lower entropy than peptides that are not CTL targeted. This correlation is independent of HLA-restriction.
Previously described HLA-B35-restricted epitope TVLDVGDAY elicited an immune response in Chinese HIV-1 positive subjects as part of peptide KKKSVTVLDVGDAYFSV.
5 of the 12 HLA-B35 carriers responded to a TVLDVGDAY-containing peptide with average magnitude of CTL response of 604 SFC/million PBMC.

References

Zhai2008 Song Zhai, Yan Zhuang, Yang Song, Shu Li, Dedong Huang, Wenzhen Kang, Xinhong Li, Qi Liao, Yanhou Liu, Zhongfang Zhao, Yichen Lu, and Yongtao Sun. HIV-1-Specific Cytotoxic T Lymphocyte (CTL) Responses Against Immunodominant Optimal Epitopes Slow the Progression of AIDS in China. Curr. HIV Res., 6(4):335-350, Jun 2008. PubMed ID: 18691032. Show all entries for this paper.

Displaying record number 420

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HXB2 Location	Pol(262-270) RT(107-115) DNA(2868..2894)	Pol Epitope Map
Author Location	RT(262-270 IIIB)
Epitope	`TVLDVGDAY`	Epitope Alignment
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 infection
Experimental methods
Keywords	review, responses in children, mother-to-infant transmission

Notes

Epitope defined in the context of the Pediatric AIDS Foundation ARIEL Project, a mother-infant HIV transmission study.
TVLDMGDAC is a naturally occurring variant that is less reactive.
Menendez-Arias1998, in a review, notes that this epitope includes a catalytic residue (Asp-110) in the active site of RT.

References

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

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

Displaying record number 421

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HXB2 Location	Pol(262-270) RT(107-115) DNA(2868..2894)	Pol Epitope Map
Author Location	Pol(262-270 IIIB)
Epitope	`TVLDVGDAY`	Epitope Alignment
		Show epitope variants
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 infection
Experimental methods
Keywords	responses in children, mother-to-infant transmission, escape

Notes

This study describes maternal CTL responses in the context of mother-to-infant transmission.
Detection of CTL escape mutants in the mother was associated with transmission, but the CTL-susceptible forms of the virus tended to be found in infected infants.
An additional variant that gave a positive CTL response: TVLDMGDAC.

References

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

Displaying record number 1423

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HXB2 Location	Pol(262-270) RT(107-115) DNA(2868..2894)	Pol Epitope Map
Author Location	Pol(262-270)
Epitope	`TVLDVGDAY`	Epitope Alignment
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

One of the 51 HIV-1 epitopes selected by Ferrari et al. as good candidate CTL epitopes for vaccines by virtue of being conserved and presented by common HLA alleles.

References

Ferrari2000 G. Ferrari, D. D. Kostyu, J. Cox, D. V. Dawson, J. Flores, K. J. Weinhold, and S. Osmanov. Identification of highly conserved and broadly cross-reactive HIV type 1 cytotoxic T lymphocyte epitopes as candidate immunogens for inclusion in Mycobacterium bovis BCG-vectored HIV vaccines. AIDS Res. Hum. Retroviruses, 16(14):1433-43, 20 Sep 2000. PubMed ID: 11018863. Show all entries for this paper.

Displaying record number 1562

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HXB2 Location	Pol(262-270) RT(107-115) DNA(2868..2894)	Pol Epitope Map
Author Location	RT(262-270 SF2)
Epitope	`TVLDVGDAY`	Epitope Alignment
Species (MHC/HLA)	human(B35)
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-B35+ individuals that had a CTL response to this epitope broken down by group: 1/2 group 1, 0/2 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 57923

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HXB2 Location	Pol(262-270) RT(107-115) DNA(2868..2894)	Pol Epitope Map
Author Location	Pol(262-270)
Epitope	`TVLDVGDAY`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 infection
Patient MHC/HLA	A02:01, A24:02, B35:01, B35:03, C03:03, C04:01
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	acute/early infection

Notes

The study tracked changes in amino acid residues across the whole genome over time during the first year of infection in 11 individuals representing 4 donor-recipient pairs and 3 independent seroconverters. 9 of the 11 individuals were enrolled during acute infection. In most cases, a single founder virus underwent selection, primarily in env and nef. Mutations were detected in the first week, and became consensus as early as 21 days post-onset of symptoms. Putative escape mutations were often rapidly replaced with mutually-exclusive mutations nearby. Escape mutations were more frequent than reversions.
Previously-documented B35-restricted epitope TVLDVGDAY was recognized by EliSpot assay in 1 HIV-positive B35-positive patient. The patient was negative at day 25, and positive by day 144 of infection.

References

Herbeck2011 Joshua T. Herbeck, Morgane Rolland, Yi Liu, Sherry McLaughlin, John McNevin, Hong Zhao, Kim Wong, Julia N. Stoddard, Dana Raugi, Stephanie Sorensen, Indira Genowati, Brian Birditt, Angela McKay, Kurt Diem, Brandon S. Maust, Wenjie Deng, Ann C. Collier, Joanne D. Stekler, M. Juliana McElrath, and James I. Mullins. Demographic Processes Affect HIV-1 Evolution in Primary Infection before the Onset of Selective Processes. J. Virol., 85(15):7523-7534, Aug 2011. PubMed ID: 21593162. Show all entries for this paper.

Displaying record number 57971

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HXB2 Location	Pol(262-270) RT(107-115) DNA(2868..2894)	Pol Epitope Map
Author Location	RT(107-115)
Epitope	`TVLDVGDAY`	Epitope Alignment
Epitope Name	TY9
Subtype	B
Species (MHC/HLA)	human(B35)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, CTL suppression of replication, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords	immunodominance, elite controllers

Notes

Immunodominant responses were identified from progressors and controllers. Epitope-specific CD8 T-cell lines from progressors and controllers had similar effector function profiles in intracellular cytokine staining assays. In contrast, CD8 T-cell lines derived from controllers showed enhanced virus suppression when compared with progressors. Virus suppression was mediated in an MHC-dependent manner and found to correlate with a polyfunctional IL-2+ CD8 T-cell response.
TVLDVGDAY was one of 15 immunodominant responses identified, and a T-cell line was isolated from a B35-positive progressor patient who was highly responsive to it.

References

Akinsiku2011 Olusimidele T. Akinsiku, Anju Bansal, Steffanie Sabbaj, Sonya L. Heath, and Paul A. Goepfert. Interleukin-2 Production by Polyfunctional HIV-1-Specific CD8 T Cells Is Associated with Enhanced Viral Suppression. J. Acquir. Immune Defic. Syndr., 58(2):132-140, 1 Oct 2011. PubMed ID: 21637109. Show all entries for this paper.

Displaying record number 61867

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HXB2 Location	Pol(262-270) RT(107-115) DNA(2868..2894)	Pol Epitope Map
Author Location
Epitope	`TVLDVGDAY`	Epitope Alignment
Epitope Name	TY9
Subtype	B
Species (MHC/HLA)	human(B*35:01)
Immunogen	HIV-1 infection, vaccine
Country	Japan
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Other
Keywords	vaccine-induced immune responses

Notes

The candidate tHIVconsvX vaccine is composed of 6 conserved Gag and Pol regions. Specific T cells - from 200 ART-naive, infected Japanese subjects previously exposed to the tHIVconsvX vaccine - that have the ability to supress HIV-1 replication were identified as recognizing 6 Pol epitopes. 6/25 epitopes (comprising 20 known and 5 novel mapped epitopes) remain associated with positive clinical outcome.
B*3501-restricted Pol epitope TVLDVGDAY was found in 15-mer peptide pairs C220/221 and C222. 1 HLA-carrying responder to the peptides was detected by EliSpot out of 20 subjects, while 8/221 Japanese subjects responded to the epitope.

References

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

Displaying record number 61893

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HXB2 Location	Pol(262-270) RT(107-115) DNA(2868..2894)	Pol Epitope Map
Author Location	RT(262-270)
Epitope	`TVLDVGDAY`	Epitope Alignment
Epitope Name	TY9
Subtype	B
Species (MHC/HLA)	human(B*35:01)
Immunogen	HIV-1 infection
Country	Japan
Experimental methods	CD8 T-cell Elispot - IFNγ, CTL suppression of replication, Intracellular cytokine staining, Tetramer binding
Keywords	escape, HLA associated polymorphism

Notes

HLA-B*3501 is known to be a detrimental allele associated with rapid progression to AIDS. CTL responses to 16 known HLA-B*3501-restricted epitopes however, were studied in 63 B*3501+ ART-naive Japanese subjects, to find B*3501-epitope-specific CTLs which can suppress HIV-1 replication. The effect of viral protective-epitope mutations associated with B*3501 were also investigated and so one mechanism of the detrimental effect of HLA-B*3501 was clarified: the Y135F mutation within NefYF9, which is selected by HLA-A*2402-restricted CTL, impairs the ability of YF9-specific CTL to suppress HIV replication both in vivo and in vitro.
PolRT epitope TVLDVGDAY (TY10) elicited CTL response in 27/63 HLA-B*3501+ HIV-1-infected ART naive Japanese subjects, but no significant association was found with suppression of pVL (plasma viral load).

References

Murakoshi2018a Hayato Murakoshi, Madoka Koyanagi, Tomohiro Akahoshi, Takayuki Chikata, Nozomi Kuse, Hiroyuki Gatanaga, Sarah L. Rowland-Jones, Shinichi Oka, and Masafumi Takiguchi. Impact of a Single HLA-A*24:02-Associated Escape Mutation on the Detrimental Effect of HLA-B*35:01 in HIV-1 Control. EBioMedicine, 36:103-112, Oct 2018. PubMed ID: 30249546. Show all entries for this paper.

Displaying record number 58653

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HXB2 Location	Pol(262-270) RT(107-115) DNA(2868..2894)	Pol Epitope Map
Author Location	Pol(262-270)
Epitope	`TVLDVGDAY`	Epitope Alignment
Epitope Name	RT TY9
Subtype	B, C
Species (MHC/HLA)	human(B*35:01)
Immunogen	HIV-1 infection
Country	Barbados, Botswana, Haiti, Japan, Mexico, South Africa, United Kingdom, United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	subtype comparisons

Notes

While host HLA Class I genotype is the major genetic determinant of HIV-1 progression to AIDS, the same HLA allele could have varying outcomes for different infecting HIV clades. Overall, p24 Gag-specific epitopes were targeted significantly more frequently by C-clade-infected B*3501-positive subjects (55%) than B-clade-carrying B*3501-subjects (31%), while Env-specific epitopes were targeted more frequently by B-clade-infected subjects.
In general HLA-B*3501-restricted epitopes, were not targeted differentially for different clades. In contrast, CTL targeting against one B*3501-restricted clade C Gag epitope, NPPIPVGDIY (NY10) but not clade B NY10, was associated with a lower viral set point and higher absolute CD4 count, i.e. better disease control. The above major result for epitope NY10 was confirmed for the B clade variant in Caucasian, Japanese and Mexican cohorts; C clade results were confirmed in South African (Durban) and Botswanan (Gaborne) cohorts.
In addition 5 new C-clade epitopes were identified.
Epitope TVLDVGDAY, RT TY9, elicited CTL response in >40% of B- and C-clade infected subjects.

References

Matthews2012 Philippa C. Matthews, Madoka Koyanagi, Henrik N. Kløverpris, Mikkel Harndahl, Anette Stryhn, Tomohiro Akahoshi, Hiroyuki Gatanaga, Shinichi Oka, Claudia Juarez Molina, Humberto Valenzuela Ponce, Santiago Avila Rios, David Cole, Jonathan Carlson, Rebecca P. Payne, Anthony Ogwu, Alfred Bere, Thumbi Ndung'u, Kamini Gounder, Fabian Chen, Lynn Riddell, Graz Luzzi, Roger Shapiro, Christian Brander, Bruce Walker, Andrew K. Sewell, Gustavo Reyes Teran, David Heckerman, Eric Hunter, Søren Buus, Masafumi Takiguchi, and Philip J. R. Goulder. Differential Clade-Specific HLA-B*3501 Association with HIV-1 Disease Outcome Is Linked to Immunogenicity of a Single Gag Epitope. J. Virol., 86(23):12643-12654, Dec 2012. PubMed ID: 22973023. Show all entries for this paper.

Displaying record number 422

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HXB2 Location	Pol(262-270) RT(107-115) DNA(2868..2894)	Pol Epitope Map
Author Location	RT(262-270 IIIB)
Epitope	`TVLDVGDAY`	Epitope Alignment
Species (MHC/HLA)	human(B*35:01)
Immunogen
Experimental methods
Keywords	optimal epitope, A-list

Notes

C. Brander notes this is a B*3501 epitope.

References

Llano2019 Anuska Llano, Samandhy Cedeño, Sandra Silva Arrieta, and Christian Brander. The 2019 Optimal HIV CTL Epitopes Update: Growing Diversity in Epitope Length and HLA restriction. 2019. Show all entries for this paper.

Displaying record number 54316

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HXB2 Location	Pol(262-270) RT(107-115) DNA(2868..2894)	Pol Epitope Map
Author Location	RT(107-115)
Epitope	`TVLDVGDAY`	Epitope Alignment
Species (MHC/HLA)	human(B*35:01)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, Cytokine production, HLA binding, Other
Keywords	vaccine-induced immune responses, HLA cross-presentation, HLA associated polymorphism

Notes

25 CTL epitopes with sequence conservation were studied. Population protection coverage (PPC) for 5 different ethnic groups in the US was estimated by combining HLA binding predictions and known HLA frequencies. HIV-1-naive individuals mounted a better response to the epitope pools than HIV-1 infected individuals.
A more detailed evaluation of HIV-naive T-cell responses was undertaken, limiting the study to only those peptides that are restricted to A*0201. Though the peptides could cross-recognize and bind different HLA, they were able to specifically lyse only cells of the same (A*0201) HLA-restriction. Thus, the CTL response was less degenerate than peptide binding to MHC.
In addition to the published restriction above, epitope TVLDVGDAY was predicted to be restricted by HLA B0702, B3501, B5102, B5103, B5301, B5401 and B5502 as well. B*1501, B*3501, B*5701, C*0304.

References

Reche2006 Pedro A. Reche, Derin B. Keskin, Rebecca E. Hussey, Petronela Ancuta, Dana Gabuzda, and Ellis L. Reinherz. Elicitation from Virus-Naive Individuals of Cytotoxic T Lymphocytes Directed against Conserved HIV-1 Epitopes. Med. Immunol., 5:1, 2006. PubMed ID: 16674822. Show all entries for this paper.

Displaying record number 53604

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HXB2 Location	Pol(262-270) RT(107-115) DNA(2868..2894)	Pol Epitope Map
Author Location	Pol(262-270)
Epitope	`TVLDVGDAY`	Epitope Alignment
Epitope Name	TY9
Subtype	B
Species (MHC/HLA)	human(B*35:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	8183A: A02:01, A03:01, B35:01, B51, C04, C06
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, Intracellular cytokine staining
Keywords	dynamics, acute/early infection

Notes

Patients with acute or early infection were shown to preferentially target variable peptides with higher entropy while those with chronic infection showed responses towards more conserved peptides with lower entropy. In longitudinally followed subjects, responses to variable proteins declined over time while responses to conserved proteins increased. The decline is suggested to be due to CTL escape.
The response to this epitope was not evident until month 20, and increased over time.

References

Bansal2005a Anju Bansal, Ethan Gough, Steffanie Sabbaj, Doug Ritter, Karina Yusim, Greg Sfakianos, Grace Aldrovandi, Richard A. Kaslow, Craig M. Wilson, Mark J. Mulligan, J. Michael Kilby, and Paul A. Goepfert. CD8 T-Cell Responses in Early HIV-1 Infection Are Skewed Towards High Entropy Peptides. AIDS, 19(3):241-250, 18 Feb 2005. PubMed ID: 15718834. Show all entries for this paper.

Displaying record number 60351

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HXB2 Location	Pol(262-270) RT(107-115) DNA(2868..2894)	Pol Epitope Map
Author Location	Pol(262-270)
Epitope	`TVLDVGDAY`	Epitope Alignment
Epitope Name	TY9
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.
TVLDVGDAY had a significantly positive association with HLA B*3502,B*3503,B*5301; it was recognized by 17/37 B*3502,B*3503,B*5301-positive subjects and 4/304 B*3502,B*3503,B*5301-negative subjects.

References

Displaying record number 58964

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HXB2 Location	Pol(262-270) RT(107-115) DNA(2868..2894)	Pol Epitope Map
Author Location	Rev(107-115)
Epitope	`TVLDVGDAY`	Epitope Alignment
Epitope Name	TY9
Subtype	B
Species (MHC/HLA)	human(B*57:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	32645: A01:01, A02:01, B08:01, B35:03, C04:01, C07:01
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	acute/early infection

Notes

The extent to which set-point viremia is affected by early HIV-infection T cell responses to either conserved or variable epitopes was studied. 23 ART-naive subjects were characterized for CTL responses for 6 months, postinfection. While most CTL responses (73/123) were targeted against variable HIV-1 epitopes, recognition of conserved epitopes (16/123) was associated with lower set point viremia. This was independent of HLA type and also functional avidity of the CTL response. Most of the conserved responses were targeted to Gag and Pol epitopes.
4/16 conserved epitopes were restricted by favorable HLA alleles, and 3 of those 4 were recognized in all subjects possessing the favorable allele. Only one conserved epitope was recognized by an unfavorable allele.
TY9, TVLDVGDAY, restricted by unfavorable allele HLA-B*3501, was one of the conserved epitopes and was recognized by patient 32645 (A*01:01, A*02G1; B*08:01, B*35:03; C*04G1, C*07G1).

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 60352

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HXB2 Location	Pol(262-270) RT(107-115) DNA(2868..2894)	Pol Epitope Map
Author Location	Pol(262-270)
Epitope	`TVLDVGDAY`	Epitope Alignment
Epitope Name	TY9
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.
TVLDVGDAY had a significantly positive association with HLA C*12; it was recognized by 3/48 C*12-positive subjects and 0/255 C*12-negative subjects.

References

Displaying record number 61474

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HXB2 Location	Pol(262-270) RT(107-115) DNA(2868..2894)	Pol Epitope Map
Author Location	Gag( 90TH_BK132, US1_GS004/7, J3222, JR-CSF, NL4-3, LAI)
Epitope	`TVLDVGDAY`	Epitope Alignment
Epitope Name	TY9
Subtype	B
Species (MHC/HLA)	human
Immunogen	in vitro stimulation or selection, HIV-1 infection, peptide-HLA interaction
Country	Canada, United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining
Keywords	assay or method development, memory cells

Notes

Using CTL clones as biosensors multiple LRA (latency reversing agents) were tested for efficacy in sensitizing latently-infected cells for recognition by HIV-epitope-specific CTLs. This novel experimental approach for evaluation of LRAs and latency reversal as well as amplified detection of CTL shock-and-kill eradication strategies identified several LRAs, viz. IL-15SA, IL-2, IL-15, prostratin, and TLR-2 ligand Pam₃CSK₄. IL-15 superagonist, ALT-803, primed the natural ex vivo resting, latent CD4+ T-cell-reservoir for CD8+ T cell recognition, at clinically achievable concentrations.
An HIV-Gag-TY9 (TVLDVGDAY) specific T-cell clone from subject OM265 was able to recognize LRA-primed HIV-latently-infected CD4+ T cells.

References

Jones2016 R. Brad Jones, Stefanie Mueller, Rachel O'Connor, Katherine Rimpel, Derek D. Sloan, Dan Karel, Hing C. Wong, Emily K. Jeng, Allison S. Thomas, James B. Whitney, So-Yon Lim, Colin Kovacs, Erika Benko, Sara Karandish, Szu-Han Huang, Maria J. Buzon, Mathias Lichterfeld, Alivelu Irrinki, Jeffrey P. Murry, Angela Tsai, Helen Yu, Romas Geleziunas, Alicja Trocha, Mario A. Ostrowski, Darrell J. Irvine, and Bruce D. Walker. A Subset of Latency-Reversing Agents Expose HIV-Infected Resting CD4+ T-Cells to Recognition by Cytotoxic T-Lymphocytes. PLoS Pathog., 12(4):e1005545, Apr 2016. PubMed ID: 27082643. Show all entries for this paper.