Search CTL/CD8+ T-Cell Epitope Database

Found 13 matching records:

Displaying record number 59804

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HXB2 Location	Pol(160-167) RT(5-12) DNA(2562..2585)	Pol Epitope Map
Author Location	Pol(160-167)
Epitope	`IETVPVKL`	Epitope Alignment
Epitope Name	IL8
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.
IETVPVKL had a significantly positive association with HLA B*1502; it was recognized by 1/1 B*1502-positive subjects and 4/264 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 59803

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HXB2 Location	Pol(160-167) RT(5-12) DNA(2562..2585)	Pol Epitope Map
Author Location	Pol(160-167)
Epitope	`IETVPVKL`	Epitope Alignment
Epitope Name	IL8
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.
IETVPVKL had a significantly positive association with HLA B*3502,B*3503,B*5301; it was recognized by 4/33 B*3502,B*3503,B*5301-positive subjects and 5/265 B*3502,B*3503,B*5301-negative subjects.

References

Displaying record number 59801

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HXB2 Location	Pol(160-167) RT(5-12) DNA(2562..2585)	Pol Epitope Map
Author Location	Pol(160-167)
Epitope	`IETVPVKL`	Epitope Alignment
Epitope Name	IL8
Species (MHC/HLA)	human(B*40)
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.
IETVPVKL had a significantly positive association with HLA B*40; it was recognized by 12/28 B*40-positive subjects and 13/313 B*40-negative subjects.

References

Displaying record number 56393

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HXB2 Location	Pol(160-167) RT(5-12) DNA(2562..2585)	Pol Epitope Map
Author Location	RT(5-12)
Epitope	`IETVPVKL`	Epitope Alignment
Epitope Name	IL8
Subtype	B
Species (MHC/HLA)	human(B*40)
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*40-associated substitutions within optimally defined epitope IETVPVKL are at positions E2 and K7, IeTVPVkL.

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 55090

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HXB2 Location	Pol(160-167) RT(5-12) DNA(2562..2585)	Pol Epitope Map
Author Location	Pol
Epitope	`IETVPVKL`	Epitope Alignment
Epitope Name	IL-8
Species (MHC/HLA)	human(B40)
Immunogen	HIV-1 infection
Experimental methods
Keywords	escape, TCR usage, mutation acquisition

Notes

The dependence of TCR clonotype recruitment on genetic background was determined by studying monozygotic twins infected with the same HIV-1 strain. After an early, initial correlation in the magnitude, specificity and immunodominance of CTL response [Draenert et al. J. Exp. Med. 203:529-539(2006)], subsequent disease was mixed with respect to CTL epitopes' mutational escape. TCR alpha and beta chain repertoires were analyzed and it was found that their clonotypes in HIV-specific CTLs were broadly heterogeneous for both concordant and discordant epitope sequence evolution between the twins. Therefore initial TCR recruitment appears to be an entirely random process independent of genetic background of the infected individual.
This epitope, IL8, showed discordant epitope evolution between the twins, and both alpha and beta TCR chains recruited were entirely different between them.

References

Yu2007 Xu G. Yu, Mathias Lichterfeld, Katie L. Williams, Javier Martinez-Picado, and Bruce D. Walker. Random T-Cell Receptor Recruitment in Human Immunodeficiency Virus Type 1 (HIV-1)-Specific CD8+ T Cells from Genetically Identical Twins Infected with the Same HIV-1 Strain. J Virol, 81(22):12666-12669, Nov 2007. PubMed ID: 17804503. Show all entries for this paper.

Displaying record number 56036

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HXB2 Location	Pol(160-167) RT(5-12) DNA(2562..2585)	Pol Epitope Map
Author Location	RT
Epitope	`IETVPVKL`	Epitope Alignment
Epitope Name	IL8(RT)
Subtype	B
Species (MHC/HLA)	human(B40)
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-B40-restricted epitope IETVPVKL elicited an immune response in Chinese HIV-1 positive subjects as part of peptide PISPIETVPVKLKPGM.
5 of the 20 HLA-B40 carriers responded to a IETVPVKL-containing peptide with average magnitude of CTL response of 664 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 52566

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HXB2 Location	Pol(160-167) RT(5-12) DNA(2562..2585)	Pol Epitope Map
Author Location	RT(5-12)
Epitope	`IETVPVKL`	Epitope Alignment
Species (MHC/HLA)	human(B*40:01)
Immunogen	HIV-1 infection
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 55060

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HXB2 Location	Pol(160-167) RT(5-12) DNA(2562..2585)	Pol Epitope Map
Author Location	Pol(160-167)
Epitope	`IETVPVKL`	Epitope Alignment
		Show epitope variants
Epitope Name	IL8
Species (MHC/HLA)	human(B*40:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	A02:01, A24:02, B40:01, B50:01, C*03, Cw4
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining
Keywords	immunodominance, escape, variant cross-reactivity

Notes

HIV-specific cellular and humoral immune responses were examined in monozygotic male twins infected simultaneously with the same virus. 15 of 17 targeted epitopes were identical in the twins, including two immunodominant responses. 3 of 4 declining responses in the twins showed mutations at the same residue. Evolving antibody responses cross-neutralized the other twin's virus. The results were compared with a third brother, infected by the twins' virus 13 months after their seroconversion. The data show similarity in disease course in persons of identical genetic background infected with the same strain of HIV-1.
This epitope, IETVPVKL (IL8), restricted by HLA-B*4001, had variants IdTVPVKL and IETVPVrL arise.

References

Draenert2006 Rika Draenert, Todd M. Allen, Yang Liu, Terri Wrin, Colombe Chappey, Cori L. Verrill, Guillem Sirera, Robert L. Eldridge, Matthew P. Lahaie, Lidia Ruiz, Bonaventura Clotet, Christos J. Petropoulos, Bruce D. Walker, and Javier Martinez-Picado. Constraints on HIV-1 Evolution and Immunodominance Revealed in Monozygotic Adult Twins Infected with the Same Virus. J. Exp. Med., 203(3):529-539, 20 Mar 2006. PubMed ID: 16533886. Show all entries for this paper.

Displaying record number 57322

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HXB2 Location	Pol(160-167) RT(5-12) DNA(2562..2585)	Pol Epitope Map
Author Location	Pol
Epitope	`IETVPVKL`	Epitope Alignment
Subtype	A, CRF02_AG, CRF06_cpx, CRF09_cpx
Species (MHC/HLA)	human(B*60)
Immunogen	HIV-1 infection
Country	Burkina Faso
Experimental methods	Other
Keywords	drug resistance

Notes

Drug-associated mutations were analyzed in HIV-1 pol gene from drug-naive patients in Burkina Faso. 12.5% of all mutations were drug resistance-associated, suggesting either transmission from an ART-treated tramsitter or prior undocumented use of ART by the subject. Subtype specific polymorphisms were also seen, some of them within CTL epitopes.
B-consensus HLA-B*60-restricted epitope IETVPVKL was found in subtype CRF02.AG, CRF06.cpx and CRF09.cpx sequences, but variant IETVPVtL was seen in subtype A.

References

Tebit2009 Denis M. Tebit, Lassana Sangaré, Fabrice Tiba, Yameogo Saydou, Aline Makamtse, Hermann Somlare, Guillaume Bado, Boris G. Kouldiaty, Inoussa Zabsonre, Sibiri L. Yameogo, Kanokporn Sathiandee, Joseph Y. Drabo, and Hans-Georg Kräusslich. Analysis of the Diversity of the HIV-1 pol Gene and Drug Resistance Associated Changes among Drug-Naïve Patients in Burkina Faso. J. Med. Virol., 81(10):1691-701, Oct 2009. PubMed ID: 19697403. Show all entries for this paper.

Displaying record number 59802

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HXB2 Location	Pol(160-167) RT(5-12) DNA(2562..2585)	Pol Epitope Map
Author Location	Pol(160-167)
Epitope	`IETVPVKL`	Epitope Alignment
Epitope Name	IL8
Species (MHC/HLA)	human(C*17)
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.
IETVPVKL had a significantly positive association with HLA C*17; it was recognized by 4/15 C*17-positive subjects and 9/298 C*17-negative subjects.

References

Displaying record number 61801

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HXB2 Location	Pol(160-167) RT(5-12) DNA(2562..2585)	Pol Epitope Map
Author Location
Epitope	`IETVPVKL`	Epitope Alignment
Epitope Name	IL8
Species (MHC/HLA)	human
Immunogen	HIV-1 infection, vaccine
Patient MHC/HLA	VID406: A03:01, A31:01, B40:01, B44:03, C03:04, C04:01, DQB102, DQB105, DRB101:01, DRB107:01, DRB4
Country	United Kingdom
Experimental methods	Intracellular cytokine staining, Other
Keywords	vaccine-induced immune responses, optimal epitope

Notes

Since CTL response in natural HIV-1 infections is mostly against variable but immunodominant epitopes, lymphocytes from 12 vaccine(HIVconsv)-exposed subjects of the HIV-CORE 002 study were used to determine and define 14 less variable but typically subdominant, optimal novel epitopes.
Epitope IETVPVKL (IL8) is within peptides KNFPISPIETVPVKLK (HC049) and SPIETVPVKLKPGMD (HC050) that was recognized by VID406, 1/12 vaccinated subjects. IL8 was previously reported to be an HLA-B*4001 restricted A-list epitope in the Los Alamos HIV Immunology database (Draenert2006 and Zhai2008).

References

Borthwick2017 Nicola Borthwick, Zhansong Lin, Tomohiro Akahoshi, Anuska Llano, Sandra Silva-Arrieta, Tina Ahmed, Lucy Dorrell, Christian Brander, Hayato Murakoshi, Masafumi Takiguchi, and Tomáš Hanke. Novel, In-Natural-Infection Subdominant HIV-1 CD8+ T-Cell Epitopes Revealed in Human Recipients of Conserved-Region T-Cell Vaccines. PLoS One, 12(4):1-19, 2017. PubMed ID: 28448594. Show all entries for this paper.

Displaying record number 62834

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HXB2 Location	Pol(160-167) RT(5-12) DNA(2562..2585)	Pol Epitope Map
Author Location	RT(5-12)
Epitope	`IETVPVKL`	Epitope Alignment
Epitope Name	IL-8
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).
RT polymorphisms E6K & V8I, as well as subtype C consensus V8, were associated with altered RC and are located within best-defined A-list epitope IETVPVK, IL-8, known to bind to B*40:01.
E6K occurred in 19 participant-derived recombinant viruses with a median RC of 0.87, while 382 analogous viruses without E6K had a median RC of 0.92, relative to unmodified NL4-3.
V8I occurred in 14 participant-derived recombinant viruses with a median RC of 0.98, while 468 analogous viruses with consensus V8 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 62873

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HXB2 Location	Pol(160-167) RT(5-12)	Pol Epitope Map
Author Location	RT(5-12)
Epitope	`IETVPVKL`	Epitope Alignment
		Show epitope variants
Epitope Name	IL8
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 Con 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 NL4-3 recombinant virus encoding wild-type SK-278 RT-integrase, the introduction of E6K mutation did not mediate a significant reduction in RC.
E6K is located within best-defined epitope IETVPVK (IL-8, known to bind to B*40:01) present in SK-278 RT.

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.