Search CTL/CD8+ T-Cell Epitope Database

Found 15 matching records:

Displaying record number 61942

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HXB2 Location	Pol(464-473) RT(309-318) DNA(3474..3503)	Pol Epitope Map
Author Location	HIV-1
Epitope	`ILKEPVHGVY`	Epitope Alignment
Epitope Name	IV9
Subtype	B
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Country	Germany
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding, Other
Keywords	assay or method development

Notes

Novel HLA-C restricted epitopes can be identified by the analysis of peptide-induced HLA-C upregulation on B-lymphoblastoid cell lines (B-LCLs) and T2-cells incubated with HIV-1 specific peptides. HLA-C-specific antibody DT9 staining and resulting mean fluorescent intensity (MFI) were used to quantify HLA-C.
Known A*02-restricted CTL Nef epitope ILKEPVHGVY did not change HLA-C expression on B-LCL cells. It was used as a negative control as it binds HLA-A*02 and not Cw*0702.

References

Stoll2015 Andrej Stoll, Silke Bergmann, Christiane Mummert, Sandra M. Mueller-Schmucker, Bernd M. Spriewald, Ellen G. Harrer, and Thomas Harrer. Identification of HLA-C Restricted, HIV-1-Specific CTL Epitopes by Peptide Induced Upregulation of HLA-C Expression. J. Immunol. Methods, 418:9-18, Mar 2015. PubMed ID: 25633660. Show all entries for this paper.

Displaying record number 62868

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HXB2 Location	Pol(464-473) RT(309-318) DNA(3474..3503)	Pol Epitope Map
Author Location	Pol
Epitope	`ILKEPVHGVY`	Epitope Alignment
Epitope Name	1249
Subtype	multiple
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	T-cell Elispot
Keywords	binding affinity, computational epitope prediction, HLA cross-presentation

Notes

Epitopes defined using sequence parsing and matching algorithm Conservatrix, and epitope prediction tool EpiMatrix, were shown to be conserved in a broad range of HIV-1 sequences derived from different parts of the world. 31 novel highly conserved HIV-1 epitopes were found, among which four were recognized as promiscuous epitopes and five as MHC supertypes.
Estimated binding probability for ILKEPVHGVY: 96% Promiscuous epitope binding to A02 and Bw62.

References

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

Displaying record number 52868

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HXB2 Location	Pol(464-473) RT(309-318) DNA(3474..3503)	Pol Epitope Map
Author Location	Pol
Epitope	`ILKEPVHGVY`	Epitope Alignment
Epitope Name	1249
Subtype	multiple
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Patient MHC/HLA	A2, A30, B39; A2, A3, B44, Cw5, Cw7; A2, A30, B35, B49, Cw4, Cw7
Country	United States
Experimental methods	T-cell Elispot
Keywords	binding affinity, computational epitope prediction, HLA cross-presentation

Notes

Epitopes defined using sequence parsing and matching algorithm Conservatrix, and epitope prediction tool EpiMatrix, were shown to be conserved in a broad range of HIV-1 sequences derived from different parts of the world. 31 novel highly conserved HIV-1 epitopes were found, among which four were recognized as promiscuous epitopes and five as MHC supertypes.
Estimated binding probability for ILKEPVHGVY: 96% Promiscuous epitope binding to A02 and Bw62.

References

Displaying record number 56389

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HXB2 Location	Pol(464-473) RT(309-318) DNA(3474..3503)	Pol Epitope Map
Author Location	RT(309-318)
Epitope	`ILKEPVHGVY`	Epitope Alignment
Epitope Name	IY10
Subtype	B
Species (MHC/HLA)	human(B*15)
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.
HLAs-B*15-associated substitution within optimally defined epitope ILKEPVHGVY is at position V9, ILKEPVHGvY.

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 52976

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HXB2 Location	Pol(464-473) RT(309-318) DNA(3474..3503)	Pol Epitope Map
Author Location	RT(309-317)
Epitope	`ILKEPVHGVY`	Epitope Alignment
Species (MHC/HLA)	human(B15)
Immunogen	HIV-1 infection
Patient MHC/HLA	A3, A32, B15, B51, C*03, Cw6, DQ7, DR4, DR8
Country	Netherlands
Experimental methods	CD8 T-cell Elispot - IFNγ, Flow cytometric T-cell cytokine assay
Keywords	rate of progression, escape

Notes

Both stable potential epitopes and epitopes with escape mutations were found in a patient with increasing viral load over a time period of 4 years. Fixation of escape mutations occurred sequentially and correlated with the rise in viral load and with the increased number of productively infected cells.
This is one of 17 potential epitopes from this individual, defined based on previously identified epitopes presented by appropriate HLA molecules. Full length genome sequence did not reveal changes in time in any of these epitopes over a four year period. Peptide pools initially revealed very little response to these epitopes, but this increased over time.

References

Geels2003 Mark J. Geels, Marion Cornelissen, Hanneke Schuitemaker, Kiersten Anderson, David Kwa, Jolanda Maas, John T. Dekker, Elly Baan, Fokla Zorgdrager, Remco van den Burg, Martijn van Beelen, Vladimir V. Lukashov, Tong-Ming Fu, William A. Paxton, Lia van der Hoek, Sheri A. Dubey, John W. Shiver, and Jaap Goudsmit. Identification of Sequential Viral Escape Mutants Associated with Altered T-Cell Responses in a Human Immunodeficiency Virus Type 1-Infected Individual. J. Virol., 77(23):12430-12440, Dec 2003. PubMed ID: 14610167. Show all entries for this paper.

Displaying record number 56002

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HXB2 Location	Pol(464-473) RT(309-318) DNA(3474..3503)	Pol Epitope Map
Author Location	RT
Epitope	`ILKEPVHGVY`	Epitope Alignment
Epitope Name	IY10(RT)
Subtype	B
Species (MHC/HLA)	human(B15)
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-B15-restricted epitope ILKEPVHGVY elicited an immune response in Chinese HIV-1 positive subjects as part of peptide ELAENREILKEPVHGVYY.
4 of the 21 HLA-B15 carriers responded to ILKEPVHGVY-containing peptide with average magnitude of CTL response of 410 SFC/million PBMC (author communication and Fig.1).

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 541

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HXB2 Location	Pol(464-473) RT(309-318) DNA(3474..3503)	Pol Epitope Map
Author Location	RT(476-485 LAI)
Epitope	`ILKEPVHGVY`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*15:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords	optimal epitope, A-list

Notes

C. Brander notes this is a B*1501 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 61168

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HXB2 Location	Pol(464-473) RT(309-318) DNA(3474..3503)	Pol Epitope Map
Author Location	Pol(464-473)
Epitope	`ILKEPVHGVY`	Epitope Alignment
		Show epitope variants
Epitope Name	IY10
Subtype	B
Species (MHC/HLA)	human(B*15:10)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Other
Keywords	acute/early infection, variant cross-reactivity

Notes

An 11-member cohort of acutely infected patients was studied to find that CTL cross-recognition of variant epitopes during acute infection is absent or poor as opposed to during chronic HIV-infection.
Pol epitope ILKEPVHGVY, IY10_464-473,-specific T cells were less cytotoxic to variants than autologous IY10 in acute infection. No variants tested cross-reacted with T cells specific to autologous IY10.

References

Du2016 Victor Y. Du, Anju Bansal, Jonathan Carlson, Jesus F. Salazar-Gonzalez, Maria G. Salazar, Kristin Ladell, Stephanie Gras, Tracy M. Josephs, Sonya L. Heath, David A. Price, Jamie Rossjohn, Eric Hunter, and Paul A. Goepfert. HIV-1-Specific CD8 T Cells Exhibit Limited Cross-Reactivity during Acute Infection. J. Immunol., 196(8):3276-3286, 15 Apr 2016. PubMed ID: 26983786. Show all entries for this paper.

Displaying record number 540

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HXB2 Location	Pol(464-473) RT(309-318) DNA(3474..3503)	Pol Epitope Map
Author Location	RT(476-485 LAI)
Epitope	`ILKEPVHGVY`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B62)
Immunogen	HIV-1 infection
Experimental methods
Keywords	review

Notes

Review of HIV CTL epitopes.

References

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

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.

Displaying record number 52440

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HXB2 Location	Pol(464-473) RT(309-318) DNA(3474..3503)	Pol Epitope Map
Author Location	Pol
Epitope	`ILKEPVHGVY`	Epitope Alignment
Subtype	A, B, D
Species (MHC/HLA)	human(B62)
Immunogen	HIV-1 infection, vaccine
Experimental methods
Keywords	subtype comparisons, epitope processing, vaccine-induced immune responses, immunodominance

Vaccine Details

Vaccine type	DNA prime with modified vaccinia Ankara (MVA) boost
Vaccine strain	A clade
Vaccine component	p17 Gag, p24 Gag

Notes

The HIV-1 subtype A focused vaccine HIVA contains p24 and p17, in a reversed order relative to the Gag polyprotein to prevent myristylation of p17, which could direct the protein to the cell membrane and inhibit efficient peptide processing and class I presentation, as well as a polyepitope string of conserved, often immunodominant epitopes that were selected to have particularly good cross-reactive potential for the A-clade epidemic in Nairobi, Kenya. A DNA and MVA prime-boost vaccination protocol using the HIVA antigen will be used in a phase III clinical trial in Kenya. This epitope is included in the polyepitope string Hanke2000.
Multiple CD4+ or CD8+ T-cell vaccine-induced responses to peptide pools were detected using intracellular cytokine staining and IFNgamma Elispot assays after vaccination of 5 macaques. The response to the Mamu A*01 SIV p27 epitope p11C (CTPYDINQM), included in the polyepitope region, was not immunodominant in the Mamu A*01 vaccinated macaques, possibly because of processing limitations in context of the artificial polyepitope string Wee2002.

References

Hanke2000 Tomas Hanke and Andrew J. McMichael. Design and construction of an experimental HIV-1 vaccine for a year-2000 clinical trial in Kenya. Nat. Med., 6(9):951-955, Sep 2000. PubMed ID: 10973301. Show all entries for this paper.

Wee2002 Edmund G.-T. Wee, Sandip Patel, Andrew J. McMichael, and Tomáš Hanke. A DNA/MVA-Based Candidate Human Immunodeficiency Virus Vaccine for Kenya Induces Multi-Specific T Cell Responses in Rhesus Macaques. J. Gen. Virol., 83(Pt 1):75-80, Jan 2002. PubMed ID: 11752703. Show all entries for this paper.

Displaying record number 58695

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HXB2 Location	Pol(464-473) RT(309-318) DNA(3474..3503)	Pol Epitope Map
Author Location	Pol
Epitope	`ILKEPVHGVY`	Epitope Alignment
		Show epitope variants
Subtype	B
Species (MHC/HLA)	human(C*03:03)
Immunogen	HIV-1 infection
Country	China
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	escape, HLA associated polymorphism

Notes

In this original study showing the protective role of HLA-C restricted CTL responses in nonwhite Chinese HIV-positive subjects, the authors find an association between a single nucleotide polymorphism (SNP) upstream of HLA-C and immune pressure on the infecting Clade B HIV. This mutation is found to correlate with enhanced cell surface HLA-C expression, lower VL, greater maintenance of CD4 cells resulting in slower progression to AIDS and now also a greater IFN-γ production by HLA-C-restricted CTLs.
The SNP is -35CC and is associated with 29% mutations in viral DNA as opposed to only 4% mutations in -35TT subjects. These mutations that were associated with the SNP in HLA-C were denoted C-mut. 6 C-mut were found in proviral DNA - 3 in previously known epitopes and 3 in peptides containing as yet unpublished epitopes.
For Pol epitope ILKEPVHGVY, C-mut is due to a K466R substitution that decreased recognition.

References

Blais2012 Marie-Eve Blais, Yonghong Zhang, Tim Rostron, Harry Griffin, Stephen Taylor, Keyi Xu, Huiping Yan, Hao Wu, Ian James, Mina John, Tao Dong, and Sarah L. Rowland-Jones. High Frequency of HIV Mutations Associated with HLA-C Suggests Enhanced HLA-C-Restricted CTL Selective Pressure Associated with an AIDS-Protective Polymorphism. J. Immunol., 188(9):4663-4670, 1 May 2012. PubMed ID: 22474021. Show all entries for this paper.

Displaying record number 61910

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HXB2 Location	Pol(464-473) RT(309-318) DNA(3474..3503)	Pol Epitope Map
Author Location	Pol
Epitope	`ILKEPVHGVY`	Epitope Alignment
		Show epitope variants
Epitope Name	Pol IY10
Species (MHC/HLA)	human(C*12:02)
Immunogen	HIV-1 infection
Experimental methods	CTL suppression of replication, HLA binding, Other
Keywords	NK cells

Notes

504 ART-naive chronically infected Japanese patients were studied in this first study of non-Caucasian, non-African populations and KIR. Two HLA-KIR combinations were found that were protective in HIV-1 infection as they influence NK cell antiviral function by altering NK cell recognition of target HIV-infected cells through KIR2DL2. HLA-C*12:02 and HLA-C*14:03 both showed effects in combination with KIR2DL2/S2 on the control of HIV-1 infection as seen by significantly lower pVL via suppression of viral replication.
Escape mutation ILKEPVHGaY of peptide epitope Pol IY10, ILKEPVHGVY, is involved in the suppression of viral proliferation by lowering the expression of restricting HLA-Cw*1202 on the surface of presenting cells. The NK cell reaction assay showed that KIR2DL2/S2+ NK cells produced significantly higher levels of immune response reaction markers after stimulation with the 9A-virus-infected over WT-infected Cw*1202-cells.

References

Lin2016 Zhansong Lin, Kimiko Kuroki, Nozomi Kuse, Xiaoming Sun, Tomohiro Akahoshi, Ying Qi, Takayuki Chikata, Takuya Naruto, Madoka Koyanagi, Hayato Murakoshi, Hiroyuki Gatanaga, Shinichi Oka, Mary Carrington, Katsumi Maenaka, and Masafumi Takiguchi. HIV-1 Control by NK Cells via Reduced Interaction between KIR2DL2 and HLA-C*12:02/C*14:03. Cell Rep., 17(9):2210-2220, 22 Nov 2016. PubMed ID: 27880898. Show all entries for this paper.

Displaying record number 58625

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HXB2 Location	Pol(464-473) RT(309-318) DNA(3474..3503)	Pol Epitope Map
Author Location	Pol(463-472)
Epitope	`ILKEPVHGVY`	Epitope Alignment
Epitope Name	Pol 463-10 or IY10
Subtype	B
Species (MHC/HLA)	human(C*12:02)
Immunogen	HIV-1 infection
Country	Japan
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, Intracellular cytokine staining, Relative replication capacity assay
Keywords	escape, optimal epitope, novel epitope, A-list

Notes

C. Brander notes that this is an optimal Cw*1202 epitope based on data from Honda2011.

References

Displaying record number 57919

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HXB2 Location	Pol(464-473) RT(309-318) DNA(3474..3503)	Pol Epitope Map
Author Location	Pol(463-472)
Epitope	`ILKEPVHGVY`	Epitope Alignment
		Show epitope variants
Epitope Name	Pol 463-10 or IY10
Subtype	B
Species (MHC/HLA)	human(C*12:02)
Immunogen	HIV-1 infection
Country	Japan
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, Intracellular cytokine staining, Relative replication capacity assay
Keywords	escape, optimal epitope, novel epitope

Notes

Two novel HLA-Cw*1202-restricted epitopes were identified and tested for the ability to select escape mutants.
Optimal epitope ILKEPVHGVY was identified by responses to overlapping peptides.
CTL clones of the epitope were able to kill Cw*1202 cells expressing HIV-1, confirming that the epitope is a naturally processed CTL epitope.
The 9A mutant was associated with Cw*1202 absence in a cohort of 108 patients. ILKEPVHGVY-specific clones effectively killed target cells infected with the WT peptide, but failed to kill those infected with 9A mutant, indicating an escape. The mutant also showed up in 4 HLA-Cw*1202 patients late time in infection, suggesting slow selection. Finally, the mutant had a higher fitness cost than WT in a competitive replication assay, and 3/5 Cw*1202- individuals showed the reversion within 2 years after 9A mutant was found.

References

Honda2011 Kazutaka Honda, Nan Zheng, Hayato Murakoshi, Masao Hashimoto, Keiko Sakai, Mohamed Ali Borghan, Takayuki Chikata, Madoka Koyanagi, Yoshiko Tamura, Hiroyuki Gatanaga, Shinichi Oka, and Masafumi Takiguchi. Selection of Escape Mutant by HLA-C-Restricted HIV-1 Pol-Specific Cytotoxic T Lymphocytes Carrying Strong Ability to Suppress HIV-1 Replication. Eur. J. Immunol., 41(1):197-106, Jan 2011. PubMed ID: 21182081. Show all entries for this paper.

Displaying record number 62846

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HXB2 Location	Pol(464-473) RT(309-318) DNA(3474..3503)	Pol Epitope Map
Author Location	RT(309-318)
Epitope	`ILKEPVHGVY`	Epitope Alignment
Epitope Name	IY10
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).
Subtype C consensus K311 was associated with altered RC and is located within RT best-defined A-list epitope ILKEPVHGVY, IY10, known to bind to A*02:01, B*15:01, & C*12:02.
Consensus K311 occurred in 458 participant-derived recombinant viruses with a median RC of 0.92, while 17 analogous viruses without K at residue 311 had a median RC of 0.89, 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.