Search CTL/CD8+ T-Cell Epitope Database

Found 17 matching records:

Displaying record number 60179

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HXB2 Location	Gag(429-437) p2p7p1p6(66-74) DNA(2074..2100)	Gag Epitope Map
Author Location	Gag(429-437)
Epitope	`RQANFLGKI`	Epitope Alignment
Epitope Name	RI9
Species (MHC/HLA)	human(B*13)
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.
RQANFLGKI had a significantly positive association with HLA B*13; it was recognized by 13/15 B*13-positive subjects and 4/326 B*13-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 54091

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HXB2 Location	Gag(429-437) p2p7p1p6(66-74) DNA(2074..2100)	Gag Epitope Map
Author Location
Epitope	`RQANFLGKI`	Epitope Alignment
Epitope Name	RI9
Species (MHC/HLA)	human(B*13)
Immunogen
Experimental methods
Keywords	optimal epitope, A-list

Notes

C. Brander notes this is a B*13 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 54583

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HXB2 Location	Gag(429-437) p2p7p1p6(66-74) DNA(2074..2100)	Gag Epitope Map
Author Location	Gag(429-437)
Epitope	`RQANFLGKI`	Epitope Alignment
Subtype	B, C
Species (MHC/HLA)	human(B*13)
Immunogen	HIV-1 infection
Patient MHC/HLA	A03:01, A30:01, B13:01, B14:02, C06:02, C08:02
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining
Keywords	epitope processing, escape, mutation acquisition, viral fitness and reversion, HLA associated polymorphism

Notes

To determine whether HLA-B*13-restricted CTL responses could partially explain low viremic loads in patients, a cohort of chronic C-clade infected subjects was studied. 6 novel B*13-restricted CTL epitopes were defined from both C- and B-clade viruses, 3 of which were within Gag. B*13-restricted CTL responses correlated with lower viremia, with most immunity targeted against Gag epitopes (p15, p17, p24). Gag epitope escape variants may exact a high viral fitness cost, mutations being seen within and around the optimal epitope.
Mutations in this epitope, RQANFLGKI, were seen at K436R i.e. to RQANFLGrI as well as at I437VLM i.e. to RQANFLGKv, RQANFLGKl and RQANFLGKm. These C-terminii variants may compromise viral fitness by interference with protease cleavage between p7 and p1.

References

Honeyborne2007 Isobella Honeyborne, Andrew Prendergast, Florencia Pereyra, Alasdair Leslie, Hayley Crawford, Rebecca Payne, Shabashini Reddy, Karen Bishop, Eshia Moodley, Kriebashnie Nair, Mary van der Stok, Noel McCarthy, Christine M. Rousseau, Marylyn Addo, James I. Mullins, Christian Brander, Photini Kiepiela, Bruce D. Walker, and Philip J. R. Goulder. Control of Human Immunodeficiency Virus Type 1 Is Associated with HLA-B*13 and Targeting of Multiple Gag-Specific CD8+ T-Cell Epitopes. J. Virol., 81(7):3667-3672, Apr 2007. PubMed ID: 17251285. Show all entries for this paper.

Displaying record number 53984

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HXB2 Location	Gag(429-437) p2p7p1p6(66-74) DNA(2074..2100)	Gag Epitope Map
Author Location	( C consensus)
Epitope	`RQANFLGKI`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*13)
Immunogen	HIV-1 infection
Country	South Africa
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, optimal epitope

Notes

A comprehensive analysis of 160 class I T cell responses in 578 individuals from KwaZulu-Natal, South Africa was performed. Gag-specific responses were associated with lowering viremia, while Env, accessory and regulatory protein-specific responses were associated with higher viremia.
RQANFLGKI is an optimal epitope.

References

Kiepiela2007 Photini Kiepiela, Kholiswa Ngumbela, Christina Thobakgale, Dhanwanthie Ramduth, Isobella Honeyborne, Eshia Moodley, Shabashini Reddy, Chantal de Pierres, Zenele Mncube, Nompumelelo Mkhwanazi, Karen Bishop, Mary van der Stok, Kriebashnie Nair, Nasreen Khan, Hayley Crawford, Rebecca Payne, Alasdair Leslie, Julia Prado, Andrew Prendergast, John Frater, Noel McCarthy, Christian Brander, Gerald H. Learn, David Nickle, Christine Rousseau, Hoosen Coovadia, James I. Mullins, David Heckerman, Bruce D. Walker, and Philip Goulder. CD8+ T-Cell Responses to Different HIV Proteins Have Discordant Associations with Viral Load. Nat. Med., 13(1):46-53, Jan 2007. PubMed ID: 17173051. Show all entries for this paper.

Displaying record number 56379

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HXB2 Location	Gag(429-437) p2p7p1p6(66-74) DNA(2074..2100)	Gag Epitope Map
Author Location	p2p7p1p6(429-437)
Epitope	`RQANFLGKI`	Epitope Alignment
Epitope Name	RI9
Subtype	B
Species (MHC/HLA)	human(B*13)
Immunogen	HIV-1 infection
Country	Australia, Canada, Germany, United States
Experimental methods
Keywords	HLA associated polymorphism

Notes

98 newly infected patients were studied to track early host HLA and Gag/Pol/Nef epitope immune responses' association with viral evolution. Response hierarchies were the same as those for later infection, and 50% of the most rapidly substituting epitopes were restricted by protective HLA, e.g. Gag B*57-associated mutations which were the most rapidly reverting upon transmission to a non-B*57-host. While there are great differences in mutation rates and reversions across the HIV proteome, most early viral change is driven by immune pressure.
HLA-driven epitope evolution was seen in 80% of published CTL epitopes.
HLA-B*13-associated substitution within optimally defined epitope RQANFLGKI is at positions K8 and I9, RQANFLGki.

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 57179

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HXB2 Location	Gag(429-437) p2p7p1p6(66-74) DNA(2074..2100)	Gag Epitope Map
Author Location	p1(429-437)
Epitope	`RQANFLGKI`	Epitope Alignment
		Show epitope variants
Epitope Name	RI9
Subtype	C
Species (MHC/HLA)	human(B*13)
Immunogen	virus
Experimental methods	Relative replication capacity assay
Keywords	escape

Notes

Immunodominant HLA-B*13-restricted Gag p1 epitope RI9, RQANFLGKI, is targeted during chronic infection and has variants I437L, RQANFLGKl; I437M, RQANFLGKm; K436R, RQANFLGrI; I437V, RQANFLGKv; RQANFLGrm; and RQANFLGrv. This is the first report of a Gag, but non-p24, epitope that can reduce viral fitness and affect immune control.
I437L and I437M mutants show reduced replication kinetics as well as decreased infectivity when compared with wild type RI9 or mutants I437V and K436R. Low fitness escapes I437L and I437M accumulated unprocessed p55 Gag protein resulting from decreased ribosomal frameshifting efficiency.

References

Prado2009 Julia G. Prado, Isobella Honeyborne, Ian Brierley, Maria Carmen Puertas, Javier Martinez-Picado, and Philip J. R. Goulder. Functional Consequences of Human Immunodeficiency Virus Escape from an HLA-B*13-Restricted CD8+ T-Cell Epitope in p1 Gag Protein. J. Virol., 83(2):1018-1025, Jan 2009. PubMed ID: 18945768. Show all entries for this paper.

Displaying record number 62547

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HXB2 Location	Gag(429-437) p2p7p1p6(66-74) DNA(2074..2100)	Gag Epitope Map
Author Location	Gag(429-437)
Epitope	`RQANFLGKI`	Epitope Alignment
Epitope Name	RI9
Subtype	B
Species (MHC/HLA)	human(B*13)
Immunogen	HIV-1 infection
Patient MHC/HLA	S00024: A02, B13, B15, C06, C07; S00039: A31, A32, B13, B35, C04, C*06
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	dynamics, chronic infection

Notes

This report analyzed 29 CTL responses against 23 HIV-1 epitopes in 9 untreated chronically infected "controllers" and identified inverse correlations between epitope variability and CTL clonal stability over time and between epitope variability and CTL clonal breadth.
Over 76 weeks, the RQANFLGKI-specific CTL clonal response in individual S00024 demonstrated a 0.22 Sorenson similarity index and a mean breadth of 4.5.
Over 43 weeks, the RQANFLGKI-specific CTL clonal response in individual S00039 demonstrated a 0.55 Sorenson similarity index and a mean breadth of 6.0.
Based on all HIV-1 subtype B sequences in LANL HIV Sequence Database at time of analysis, RQANFLGKI had a Simpson diversity index of 0.24.

References

Balamurugan2017 Arumugam Balamurugan, Deon Claiborne, Hwee L. Ng, and Otto O. Yang. HIV-1 Epitope Variability Is Associated with T Cell Receptor Repertoire Instability and Breadth. J. Virol., 91(16), 15 Aug 2017. PubMed ID: 28592539. Show all entries for this paper.

Displaying record number 55986

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HXB2 Location	Gag(429-437) p2p7p1p6(66-74) DNA(2074..2100)	Gag Epitope Map
Author Location	p2p7p1p6
Epitope	`RQANFLGKI`	Epitope Alignment
Epitope Name	RI9(p2p7p1p6)
Subtype	B
Species (MHC/HLA)	human(B13)
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-B13-restricted epitope RQANFLGKI elicited an immune response in Chinese HIV-1 positive subjects as part of peptides QMKDCTERQANFLGKIW and RQANFLGKIWPSHKGR.
9 of the 29 HLA-B13 carriers responded to RQANFLGKI-containing peptide #59 with average magnitude of CTL response of 342 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 58785

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HXB2 Location	Gag(429-437) p2p7p1p6(66-74) DNA(2074..2100)	Gag Epitope Map
Author Location	p15(429-437)
Epitope	`RQANFLGKI`	Epitope Alignment
Species (MHC/HLA)	human(B*13:02)
Immunogen
Experimental methods
Keywords	review

Notes

The authors review the interaction between HLA-B alleles and epitopes that are able to control viral evolution.
p15 Gag epitope RQANFLGKI has residue QML at position P2, binding to HLA pocket B and residue LIV at the C-terminal, binding to HLA pocket F. Restricting HLA is B*1302 [Honeyborne et al. JVI 81:3667-3672 (2007)].

References

Goulder2012 Philip J. R. Goulder and Bruce D. Walker. HIV and HLA Class I: An Evolving Relationship. Immunity, 37(3):426-440, 21 Sep 2012. PubMed ID: 22999948. Show all entries for this paper.

Displaying record number 58978

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HXB2 Location	Gag(429-437) p2p7p1p6(66-74) DNA(2074..2100)	Gag Epitope Map
Author Location	Gag(429-437)
Epitope	`RQANFLGKI`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(B*13:02)
Immunogen	HIV-1 infection
Country	Australia, Canada, Spain, Switzerland
Experimental methods	Other
Keywords	mutation acquisition

Notes

Computational genome-wide scans were run to find associations between (subjects' ) host genome DNA polymorphisms, and infecting HIV-1 genome sequence variation from 1071 subjects, as well as their viral load (VL). Such genome-to-genome approaches also reveal sites of single nucleotide polymorphisms (SNPs) linked to variant HIV-1 amino acids that either limit viral efficiency or that are easily tolerated by it.
48 amino acid residues of HIV-1 were linked to human SNPs, and the variants were not antiretroviral drug resistance mutations. 50% of these viral amino acids were located within previously defined optimal epitopes, such as RQANFLGKI, whose variation at position 437 is associated with SNP rs34268928.

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 61224

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HXB2 Location	Gag(429-437) p2p7p1p6(66-74) DNA(2074..2100)	Gag Epitope Map
Author Location	Gag(429-437)
Epitope	`RQANFLGKI`	Epitope Alignment
		Show epitope variants
Epitope Name	RI9
Subtype	B
Species (MHC/HLA)	human(B*13:02)
Immunogen	HIV-1 infection
Experimental methods	Relative replication capacity assay
Keywords	escape, novel epitope

Notes

Protective HLA-B*13 was studied by following the 10 most common polymorphisms associated with it. Conserved Gag and Nef B*13-restricted epitopes were shown to have fitness costs when mutated and this makes B*13 a highly protective HLA. In addition, escape-substitutions E24Q and Q107R together, but not separately, impair the ability of Nef to downregulate the MHCI molecule. A novel B*13-restricted Gag p24 epitope GQMVHQAI was identified. Also, Gag-K436R is a compensatory mutation to escape GagI437L.
Epitope RI8, RQANFLGKI, contains the escapes Gag-I437L and Gag-K436R, where K436R is a compensatory mutation.

References

Shahid2015 Aniqa Shahid, Alex Olvera, Gursev Anmole, Xiaomei T. Kuang, Laura A. Cotton, Montserrat Plana, Christian Brander, Mark A. Brockman, and Zabrina L. Brumme. Consequences of HLA-B*13-Associated Escape Mutations on HIV-1 Replication and Nef Function. J. Virol., 89(22):11557-11571, Nov 2015. PubMed ID: 26355081. Show all entries for this paper.

Displaying record number 61572

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HXB2 Location	Gag(429-437) p2p7p1p6(66-74) DNA(2074..2100)	Gag Epitope Map
Author Location	Gag(429-437)
Epitope	`RQANFLGKI`	Epitope Alignment
Species (MHC/HLA)	human(B*13:02)
Immunogen	vaccine
Experimental methods	Other
Keywords	review, vaccine-induced immune responses, vaccine antigen design, protective allele

Notes

This review refocuses attention on host protective HLA/ MHC class I molecules after the failure of the 2007 Merck & Co. Inc. as well as the impending 2008 Vaccine Research Center (VRC) vaccines.
Gag epitope RQANFLGKI is associated with slow progression and low viral set point( J. Prado, personal communication; [Honeyborne et al. J. Virol. 81:3667-3672 (2007)]; [Harrer et al. AIDS. 19:734-735 (2005)]).

References

Goulder2008 Philip J. R. Goulder and David I. Watkins. Impact of MHC Class I Diversity on Immune Control of Immunodeficiency Virus Replication. Nat. Rev. Immunol., 8(8):619-630, Aug 2008. PubMed ID: 18617886. Show all entries for this paper.

Displaying record number 60180

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HXB2 Location	Gag(429-437) p2p7p1p6(66-74) DNA(2074..2100)	Gag Epitope Map
Author Location	Gag(429-437)
Epitope	`RQANFLGKI`	Epitope Alignment
Epitope Name	RI9
Species (MHC/HLA)	human(B*15:24)
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.
RQANFLGKI had a significantly positive association with HLA B*1524; it was recognized by 1/1 B*1524-positive subjects and 1/310 B*1524-negative subjects.

References

Displaying record number 57325

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HXB2 Location	Gag(429-437) p2p7p1p6(66-74) DNA(2074..2100)	Gag Epitope Map
Author Location
Epitope	`RQANFLGKI`	Epitope Alignment
Epitope Name	Gag429-437
Subtype	B
Species (MHC/HLA)	human(B*48:01)
Immunogen	HIV-1 infection
Country	Japan
Experimental methods	Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords	optimal epitope

Notes

Study identified 2 novel HLA-B*4801-restricted epitopes, using overlapping 17-mers spanning Pol, Gag and Nef. HLA-B*4801 is frequent in Asian populations and rare in Caucasian or African populations. Optimal epitopes were identified by truncation. An IFN-γ staining assay revealed that both epitopes were naturally processed and presented by HLA-B*4801.
5/7 B*4801-positive HIV-1-infected subjects reacted to optimal epitope RQANFLGKI.

References

Murakoshi2009 Hayato Murakoshi, Mitsutaka Kitano, Tomohiro Akahoshi, Yuka Kawashima, Sachi Dohki, Shinichi Oka, and Masafumi Takiguchi. Identification and Characterization of 2 HIV-1 Gag Immunodominant Epitopes Restricted by Asian HLA Allele HLA-B*4801. Hum. Immunol., 70(3):170-174, Mar 2009. PubMed ID: 19167445. Show all entries for this paper.

Displaying record number 58618

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HXB2 Location	Gag(429-437) p2p7p1p6(66-74) DNA(2074..2100)	Gag Epitope Map
Author Location
Epitope	`RQANFLGKI`	Epitope Alignment
Epitope Name	Gag429-437
Subtype	B
Species (MHC/HLA)	human(B*48:01)
Immunogen	HIV-1 infection
Country	Japan
Experimental methods
Keywords	optimal epitope, A-list

Notes

C. Brander noted this as an optimal B*4801 epitope based on data from Murakoshi2009.

References

Displaying record number 60181

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HXB2 Location	Gag(429-437) p2p7p1p6(66-74) DNA(2074..2100)	Gag Epitope Map
Author Location	Gag(429-437)
Epitope	`RQANFLGKI`	Epitope Alignment
Epitope Name	RI9
Species (MHC/HLA)	human(B*52)
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.
RQANFLGKI had a significantly positive association with HLA B*52; it was recognized by 2/15 B*52-positive subjects and 2/311 B*52-negative subjects.

References

Displaying record number 62831

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HXB2 Location	Gag(429-437) p2p7p1p6(66-74) DNA(2074..2100)	Gag Epitope Map
Author Location	p2p7p1p6(429-437)
Epitope	`RQANFLGKI`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human
Immunogen	engineered
Experimental methods	Other, Relative replication capacity assay
Keywords	assay or method development, protective allele

Notes

NL4-3 Gag polyprotein random mutagenesis, high-throughput fitness profiling and in silico prediction of MHC-peptide binding affinity revealed that mutations in CTL epitopes presented by protective MHC-I alleles, vs. non-protective alleles, showed greater loss of experimental replicative capacity and lower levels of predicted reduction in MHC-I binding affinity. Together, these two variables could predict protectiveness of MHC-I alleles in a linear regression model. Analyses of intraperson viral evolution in 4 LTNP vs. 4 paired progressor subjects further supported paper conclusions.
After mutagenesis and passaging through human T cells, 60 single nucleotide mutations were observed in epitope RQANFLGKI (known to bind to B13 & B4801) with a log transformation of mean fitness score, relative to NL4-3, of -0.4742.

References

Du2017 Yushen Du, Tian-Hao Zhang, Lei Dai, Xiaojuan Zheng, Aleksandr M. Gorin, John Oishi, Ting-Ting Wu, Janice M. Yoshizawa, Xinmin Li, Otto O. Yang, Otoniel Martinez-Maza, Roger Detels, and Ren Sun. Effects of Mutations on Replicative Fitness and Major Histocompatibility Complex Class I Binding Affinity Are Among the Determinants Underlying Cytotoxic-T-Lymphocyte Escape of HIV-1 Gag Epitopes. mBio, 8(6), 28 Nov 2017. PubMed ID: 29184023. Show all entries for this paper.