Search CTL/CD8+ T-Cell Epitope Database

Found 12 matching records:

Displaying record number 55756

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HXB2 Location	Gag(77-85) p17(77-85) DNA(1018..1044)	Gag Epitope Map
Author Location	Gag
Epitope	`SLFNTVATL`	Epitope Alignment
Epitope Name	SFL9
Species (MHC/HLA)	human(A*02)
Immunogen
Experimental methods	Other
Keywords	TCR usage

Notes

TCR can recognize multiple and distinct ligands. A model of TCR peptide recognition using amino acid similarity matrices is developed here, to predict cross-reactivity within diverse CTL epitopes. The ability of TCRs to recognize unrelated peptides with high specificity is termed "poly-specificity" here.
Non-immunogenic HIV peptides were found to be similar to human self-antigens, suggesting that sequence similarity to self-antigens is what discriminates between immunodominant and cryptic epitope-elicited CTL responses.
TCR specificity is position dependent in SLFNTVATL, similar aa substitutions usually do not affect TCR recognition of epitopes. In this epitope, position 1 is consistently of less importance and can tolerate mutation. Position 5, however, can only tolerate one possible mutation, T5S, to SLFNsVATL. Postions 2-6, and 8-9 are most important for peptide recognition and positions 2 and 9 determine peptide binding.

References

Frankild2008 Sune Frankild, Rob J. de Boer, Ole Lund, Morten Nielsen, and Can Kesmir. Amino Acid Similarity Accounts for T Cell Cross-Reactivity and for ``holes'' in the T Cell Repertoire. PLoS ONE, 3(3):e1831, 2008. PubMed ID: 18350167. Show all entries for this paper.

Displaying record number 57623

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HXB2 Location	Gag(77-85) p17(77-85) DNA(1018..1044)	Gag Epitope Map
Author Location	p17
Epitope	`SLFNTVATL`	Epitope Alignment
Subtype	A
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Country	United Kingdom
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	vaccine-induced immune responses

Notes

MVA/HIV-1 vaccines were given to both HIV-negative and -positive subjects. Since vector-specific T-cell responses were of low magnitude and duration (peaking 2-4 weeks after second vaccination) and did not out-grow HIV-specific CTL responses, MVA is considered an attractive vector for HIV-1 vaccinations.
Stronger post-vaccination responses to MVA were seen in HIV-1+ subjects than in HIV-infected subjects.
In one subject, 016, HLA-A2-restricted MVA epitope elicited greater CTL response than HLA-A2-restricted Gag p17 epitope, SFLNTVATL. In subject 018, however, CTL responses to MVA epitope TYNDHIVNL and to HIV-1 SLFNTVATL were similar in magnitude and kinetics.

References

Howles2010 Sarah Howles, Ana Guimarães-Walker, Hongbing Yang, Gemma Hancock, Katalin di Gleria, Tony Tarragona-Fiol, Peter Hayes, Jill Gilmour, Anne Bridgeman, Tomáš Hanke, Andrew McMichael, and Lucy Dorrell. Vaccination with a Modified Vaccinia Virus Ankara (MVA)-Vectored HIV-1 Immunogen Induces Modest Vector-Specific T Cell Responses in Human Subjects. Vaccine, 28(45):7306-7312, 21 Oct 2010. PubMed ID: 20816902. Show all entries for this paper.

Displaying record number 56349

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HXB2 Location	Gag(77-85) p17(77-85) DNA(1018..1044)	Gag Epitope Map
Author Location	Gag(77-85)
Epitope	`SLFNTVATL`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Country	Canada, South Africa
Experimental methods
Keywords	escape

Notes

A statistical model, the phylogenetic dependency network (PDN), was developed to differentiate the confounding effects of codon variation, linkage disequilibrium of HLA alleles and HIV phylogeny from HLA-associated evolution including HIV selection by HLA-pressure and codon evolution.
This approach was applied to 2 cohorts of 1144 Gag sequences from HIV-infected individuals, generating associations between HIV codons themselves and codons with HLA alleles. Results generated predicted escapes that confirmed that escape kinetics and compensating mutations are consistent across clades. General patterns of covariation and CTL adaptation were determined. Some clade-based differences were identified.
HLA-A*02-restricted, clade C consensus SL9, SLFNTVATL, has previously reported escapes that PDN did not find.

References

Carlson2008 Jonathan M. Carlson, Zabrina L. Brumme, Christine M. Rousseau, Chanson J. Brumme, Philippa Matthews, Carl Kadie, James I. Mullins, Bruce D. Walker, P. Richard Harrigan, Philip J. R. Goulder, and David Heckerman. Phylogenetic Dependency Networks: Inferring Patterns of CTL Escape and Codon Covariation in HIV-1 Gag. PLoS Comput Biol, 4(11):e1000225, Nov 2008. PubMed ID: 19023406. Show all entries for this paper.

Displaying record number 59229

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HXB2 Location	Gag(77-85) p17(77-85) DNA(1018..1044)	Gag Epitope Map
Author Location	Gag(77-85)
Epitope	`SLFNTVATL`	Epitope Alignment
		Show epitope variants
Subtype	B
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Patient MHC/HLA	Subject 8: A02:01, A24:02, B07:02, B40:01, C03:04, C07:02
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding
Keywords	dynamics, acute/early infection, dendritic cells

Notes

Variants of Gag, Env, and Nef epitopes were studied in one subject over >10 years of infection. A set of known HLA A*0201- and B*0702-restricted epitopes, plus additional predicted epitopes, was assembled. Epitope and variant responses were studied from 4 timepoints post-seroconversion (SC): early infection post-SC (0-2.8 yrs), late infection post-SC (3.25-7.8 yrs), early ART treatment (8.3-10.1 yrs), and late ART treatment. Despite evolutionary changes, CD8+ T cells could still be primed to HIV-1 variants. The percent of epitope variants inducing HIV-1-specific memory T cell responses peaked early post-SC, then declined and remained minimal shortly after establishment of viral set point. Peptide variants with medium binding affinity were more frequent than variants with low or high binding affinity but variants with different MHC class I binding capabilities induced equally broad memory T cell responses. A trimodal pattern in the breadth of T cell memory was seen, at early SC before viral set point, and then two peaks during later infection prior to commencing cART.
SLFNTVATL was 1 of 7 epitopes with a positive correlation between predicted and observed MHC affinity. SLFNTVATL had a pattern of transient changes in the dominance of variants, with the founder variant eventually being more dominant. T-cell memory responses to SLFNTVATL were detected early post-SC, late post-SC, and during early ART treatment.

References

Melhem2014 Nada M Melhem, Kellie N. Smith, Xiao-Li Huang, Bonnie A Colleton, Weimin Jiang, Robbie B. Mailliard, James I. Mullins, and Charles R. Rinaldo. The Impact of Viral Evolution and Frequency of Variant Epitopes on Primary and Memory Human Immunodeficiency Virus Type 1-Specific CD8+ T Cell Responses. Virology, 450-451:34-48, Feb 2014. PubMed ID: 24503065. Show all entries for this paper.

Displaying record number 55362

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HXB2 Location	Gag(77-85) p17(77-85) DNA(1018..1044)	Gag Epitope Map
Author Location	(77-85)
Epitope	`SLFNTVATL`	Epitope Alignment
Epitope Name	3F
Species (MHC/HLA)	human(A*02:01)
Immunogen	in vitro stimulation or selection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, HLA binding, Tetramer binding
Keywords	binding affinity, immunodominance, dendritic cells

Notes

CTL responses to the rarely recognized, subdominant HLA-A2-restricted Gag p24 epitope TLNAWKVV (TV9) were studied since its functional sensitivity and viral suppression is relatively high compared to other, dominant HLA-A2-restricted HIV-1 epitopes. Subdominant CTL responses to TV9 were not related to immunogenicity, availability of cognate TCR repertoires or HLA-epitope binding avidity.
This epitope, 3F, SLFNTVATL, is the HIV-1 Gag variant of SLYNTVATL. 3F-specific CTLs bound tetramers as a single, homogeneous population, indicating distinct avidity to 3F.

References

Schaubert2007 Keri L. Schaubert, David A. Price, Nicole Frahm, Jinzhu Li, Hwee L. Ng, Aviva Joseph, Elyse Paul, Biswanath Majumder, Velpandi Ayyavoo, Emma Gostick, Sharon Adams, Francesco M. Marincola, Andrew K. Sewell, Marcus Altfeld, Jason M. Brenchley, Daniel C. Douek, Otto O. Yang, Christian Brander, Harris Goldstein, and June Kan-Mitchell. Availability of a Diversely Avid CD8+ T Cell Repertoire Specific for the Subdominant HLA-A2-Restricted HIV-1 Gag p24(19-27) Epitope. J. Immunol., 178(12):7756-7766, 15 Jun 2007. PubMed ID: 17548613. Show all entries for this paper.

Displaying record number 102

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HXB2 Location	Gag(77-85) p17(77-85) DNA(1018..1044)	Gag Epitope Map
Author Location	p17(77-85 subtype A)
Epitope	`SLFNTVATL`	Epitope Alignment
		Show epitope variants
Epitope Name	SL9
Subtype	A
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords	subtype comparisons

Notes

CTL responses in three individuals with non-clade B infections were studied, two with subtype A infections, one with subtype C -- their infections all originated in East Africa.
This epitope is most commonly SLYNTVATL in B subtype, and CTL from the C subtype infection did not recognize B clade gag or the 3Y form of the epitope, but did recognize the predominant A and C clade form, SLFNTVATL.

References

Dorrell1999 L. Dorrell, T. Dong, G. S. Ogg, S. Lister, S. McAdam, T. Rostron, C. Conlon, A. J. McMichael, and S. L. Rowland-Jones. Distinct Recognition of Non-Clade B Human Immunodeficiency Virus Type 1 Epitopes by Cytotoxic T Lymphocytes Generated from Donors Infected in Africa. J. Virol., 73:1708-1714, 1999. PubMed ID: 9882385. Show all entries for this paper.

Displaying record number 54763

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HXB2 Location	Gag(77-85) p17(77-85) DNA(1018..1044)	Gag Epitope Map
Author Location	Gag
Epitope	`SLFNTVATL`	Epitope Alignment
Epitope Name	A2-SL9 Gag (77-85)
Subtype	B
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Patient MHC/HLA	A2, A3, B60, B7
Country	France
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	binding affinity, immunodominance, TCR usage, characterizing CD8+ T cells

Notes

Since it is suggested that a single response to B27-KK10 epitope may be responsible for the association of HLA-B*2705 patients with AIDS-free survival, B27-KK10-specific CTLs were compared to other HLA-specific CTLs in phenotype, function, clonal diversity, and antigen sensitivity in 47 treatment-naive infected slow or nonprogressing patients.
cVL, the cell-associated viral load (number of infected cells harboring HIV DNA) correlated inversely with Gag-specific CTLs. This was most significant in HLA-B27 donors, and KK10 was identified as the peptide generating strongest CTL responses.
SLFNTVATL was a dominant epitope found in non-B27-KK10 CTL responses.

References

Almeida2007 Jorge R. Almeida, David A. Price, Laura Papagno, Zaïna Aït Arkoub, Delphine Sauce, Ethan Bornstein, Tedi E. Asher, Assia Samri, Aurélie Schnuriger, Ioannis Theodorou, Dominique Costagliola, Christine Rouzioux, Henri Agut, Anne-Geneviève Marcelin, Daniel Douek, Brigitte Autran, and Victor Appay. Superior Control of HIV-1 Replication by CD8+ T Cells Is Reflected by their Avidity, Polyfunctionality, and Clonal Turnover. J. Exp. Med., 204(10):2473-2485, 1 Oct 2007. PubMed ID: 17893201. Show all entries for this paper.

Displaying record number 53411

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HXB2 Location	Gag(77-85) p17(77-85) DNA(1018..1044)	Gag Epitope Map
Author Location	p17(77-85)
Epitope	`SLFNTVATL`	Epitope Alignment
		Show epitope variants
Epitope Name	SLF
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Patient MHC/HLA	A2, A68.1, B07, B35:03, C04:01, C07:02, DQ2, DQ6, DR15, DR17, DR51, DR52
Experimental methods	CD4 T-cell Elispot - IFNγ, CD8 T-cell Elispot - IFNγ, Tetramer binding
Keywords	rate of progression, immunodominance, escape

Notes

The increase in plasma viral load in a patient that progressed rapidly was preceded by positive selection of viral escape mutations in epitopes targeted by dominant HIV-1-specific CD8+ T-cell responses, and a decrease in HIV-1-specific CD4+ and CD8+ T-cell frequencies. Overall, escape variant epitopes were recognized 0-80% as efficiently as the index peptide, and the relatively efficiency of the variant epitopes increased using PBLs collected after their appearance. No changes were found in viral tropism, replication kinetics and neutralizing antibody titers, so the rapid decline of the patient was attributed to loss of HIV containment due to CTL escape.
This epitope was one of six epitopes found to be under positive selection for escape mutations and was completely replaced by escape variants between days 327 and 635 (slYntvatl and slYnAvatl).

References

Oxenius2004 Annette Oxenius, David A. Price, Alexandra Trkola, Charles Edwards, Emma Gostick, Hua-Tang Zhang, Philippa J. Easterbrook, Tin Tun, Andrew Johnson, Anele Waters, Edward C. Holmes, and Rodney E. Phillips. Loss of Viral Control in Early HIV-1 Infection Is Temporally Associated with Sequential Escape from CD8+ T Cell Responses and Decrease in HIV-1-Specific CD4+ and CD8+ T Cell Frequencies. J. Infect. Dis., 190(4):713-721, 15 Aug 2004. PubMed ID: 15272399. Show all entries for this paper.

Displaying record number 57213

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HXB2 Location	Gag(77-85) p17(77-85) DNA(1018..1044)	Gag Epitope Map
Author Location	Gag
Epitope	`SLFNTVATL`	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Country	Kenya
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	mother-to-infant transmission

Notes

HIV-1 peptide-specific IFN-γ responses were measured over the first year of life for vertically-infected infants. Late-infected infants (between months 1 and 12) had responses that were more rapid and more focused than those infected before 1 month of life.
1/4 infants tested recognized SLF/YNTVATL.
Variants if this peptide were SLF/YNTVATL (SLfNTVATL and SLyNTVATL).

References

Lohman-Payne2009 B. Lohman-Payne, J. A. Slyker, B. A. Richardson, C. Farquhar, M. Majiwa, E. Maleche-Obimbo, D. Mbori-Ngacha, J. Overbaugh, S. Rowland-Jones, and G. John-Stewart. Infants with Late Breast Milk Acquisition of HIV-1 Generate Interferon-gamma Responses More Rapidly than Infants with Early Peripartum Acquisition. Clin. Exp. Immunol., 156(3):511-517, Jun 2009. PubMed ID: 19438605. Show all entries for this paper.

Displaying record number 1649

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HXB2 Location	Gag(77-85) p17(77-85) DNA(1018..1044)	Gag Epitope Map
Author Location	p17(77-85)
Epitope	`SLFNTVATL`	Epitope Alignment
		Show epitope variants
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 exposed seronegative, HIV-1 infection
Experimental methods
Keywords	subtype comparisons, HIV exposed persistently seronegative (HEPS), immunodominance

Notes

Variants SL(F/Y)NTVATL are A/B clade specific.
ELISPOT was used to study CTL responses to a panel of 54 predefined HIV-1 epitopes in 91 HIV-1-exposed, persistently seronegative (HEPS) and 87 HIV-1-infected female Nairobi sex workers.
Responses in HEPS women tended to be lower, and focused on different epitopes with HLA presenting molecules that have previously been associated with reduced risk of infection, and there was a shift in the response in the HEPS women upon late seroconversion to epitopes recognized by the HIV-1 infected women.
43/91 HEPS women had CD8+ responses and detection of HIV-1-specific CTL in HEPS women increased with the duration of viral exposure.
Among HLA-A2 women, 1/10 HEPS and 22/26 HIV-1 infected women recognized this epitope, likelihood ratio 18.3, p value < 0.003, and ILK(D/E)PVHGV tended to be more reactive in HEPS women, SL(F/Y)NTVATL in infected women.
The dominant response to this HLA allele was to this epitope in the 1/10 HEPS case and in 18 of the 22/26 HIV-1 infected women that responded.
Differences in epitope specificity were only seen for responses restricted by class I HLA alleles A2, A24, A*6802, B14, and B18, previously shown to be associated with resistance to HIV-1 in this cohort.
Subject ML 1250 had an A2 response to ILK(D/E)PVHGV prior to seroconversion, which switched to SL(F/Y)NTVATL post-seroconversion.
Subjects ML 1575 and ML 1592 had no response to SL(F/Y)NTVATL prior to seroconversion, but made responses post-seroconversion.
Subject ML 1760 had an A2 response to ILK(D/E)PVHGV prior to seroconversion, and gained responses to epitopes A2 SL(F/Y)NTVATL and B27 KRWII(L/M)GLNK post-seroconversion.

References

Kaul2001a R. Kaul, T. Dong, F. A. Plummer, J. Kimani, T. Rostron, P. Kiama, E. Njagi, E. Irungu, B. Farah, J. Oyugi, R. Chakraborty, K. S. MacDonald, J. J. Bwayo, A. McMichael, and S. L. Rowland-Jones. CD8(+) lymphocytes respond to different HIV epitopes in seronegative and infected subjects. J. Clin. Invest., 107(10):1303-10, May 2001. URL: http://www.jci.org/cgi/content/full/107/10/1303. PubMed ID: 11375420. Show all entries for this paper.

Displaying record number 55409

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HXB2 Location	Gag(77-85) p17(77-85) DNA(1018..1044)	Gag Epitope Map
Author Location
Epitope	`SLFNTVATL`	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	peptide-HLA interaction
Experimental methods
Keywords	HLA cross-presentation

Notes

Degenerate CTL recognition of pMHC if predictable may be used to broaden vaccine reactivity. A series of epitope-position specific substitution matrices (EPSSMs) were derived by comparing observed- versus chance-amino acid substitution frequencies.
EPSSMs showed position-specific preferences: anchor position substitutions and substitutions to P at position 1 are not well tolerated while a change to W at position 3 is favored.
All possible single mutations in Gag SLFNTVATL were experimentally checked for tolerated versus escape substitutions. EPSSMs predicted tolerated variants very well, but in the middle region of epitopes escape mutation prediction was poor.
From a dataset of cross-reactive variant epitopes, substitution types were identified. Variation in certain amino acid types were tolerated with strong position-preference. At anchor position 2, substitutions between basic amino acids are tolerated and at anchor 9, changes between aromatic and small hydrophobic amino acids. At all positions, the best tolerated substitutions were small hydrophobic residues for hydrophilic, suggesting spatial constraint and supporting use of side-chain volume as a predictor of degenerate recognition by CTLs.

References

Li2008 Fusheng Li, Denise M. McKenney, Uma Malhotra, Claire Crimi, Jessica Nolin, Lawrence Corey, Juliana M. McElrath, Mark J. Newman, and Steven G. Self. Towards Prediction of Degenerate CTL Epitope Recognition. Hum. Vaccin., 4(2):115-121, Mar-Apr 2008. PubMed ID: 18382130. Show all entries for this paper.

Displaying record number 55762

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HXB2 Location	Gag(77-85) p17(77-85) DNA(1018..1044)	Gag Epitope Map
Author Location	p17
Epitope	`SLFNTVATL`	Epitope Alignment
Epitope Name	SL9(p17)
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	China
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	immunodominance, optimal epitope, 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.
Author defined epitope SLFNTVATL elicited an immune response as part of peptide TGSEELRSLFNTVATLY. The tested sequence corresponds to previously described HLA-A2-restricted epitope SLYNTVATL, differing from this epitope, SLfNTVATL, at one residue.
11 of the 55 HLA-A2 carriers responded to SLfNTVATL-containing peptide with average magnitude of CTL response of 227 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.