Search CTL/CD8+ T-Cell Epitope Database

Found 17 matching records:

Displaying record number 150

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HXB2 Location	Gag(151-159) p24(19-27) DNA(1240..1266)	Gag Epitope Map
Author Location	p24(151-159)
Epitope	`TLNAWVKVV`	Epitope Alignment
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART, immunodominance

Notes

The single cell ELISPOT assay was optimized and highly specific, and found to work well even after the primary cells had been frozen and thawed.
Increases in gamma interferon producing cells were observed in response to anti-retroviral therapy using single cell IFN-gamma-production ELISPOT.
In 3/3 HLA-A*02, -B*27 subjects the immunodominant epitope was against HLA B*27 Gag p24 epitope KRWIILGL, not A2 Gag epitopes.

References

Huang2000 X. L. Huang, Z. Fan, C. Kalinyak, J. W. Mellors, and C. R. Rinaldo. CD8+ T Cell Gamma Interferon Production Specific for Human Immunodeficiency Virus Type 1 (HIV-1) in HIV-1-Infected Subjects. Clin. Diagn. Lab. Immunol., 7:279-287, 2000. PubMed ID: 10702505. Show all entries for this paper.

Displaying record number 1403

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HXB2 Location	Gag(151-159) p24(19-27) DNA(1240..1266)	Gag Epitope Map
Author Location	p24(151-159)
Epitope	`TLNAWVKVV`	Epitope Alignment
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Experimental methods
Keywords	HAART, ART

Notes

Administration of triple-drug antiretroviral therapy (IDV, 3TC and ZDV) sometimes showed a transient increase and other times failed to increase CTL responses in patients with advanced HIV disease, but there is a stable population of tetramer stained HIV-specific CD8+ CD45RO+ cells that can persist after therapy and long periods of virus being below the level of detection.

References

Rinaldo2000 C. R. Rinaldo, Jr., X. L. Huang, Z. Fan, J. B. Margolick, L. Borowski, A. Hoji, C. Kalinyak, D. K. McMahon, S. A. Riddler, W. H. Hildebrand, R. B. Day, and J. W. Mellors. Anti-human immunodeficiency virus type 1 (HIV-1) CD8(+) T-lymphocyte reactivity during combination antiretroviral therapy in HIV-1-infected patients with advanced immunodeficiency. J. Virol., 74(9):4127-38, May 2000. URL: http://jvi.asm.org/cgi/content/full/74/9/4127. PubMed ID: 10756025. Show all entries for this paper.

Displaying record number 54557

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HXB2 Location	Gag(151-159) p24(19-27) DNA(1240..1266)	Gag Epitope Map
Author Location	Gag(151-159)
Epitope	`TLNAWVKVV`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	Intracellular cytokine staining, Other
Keywords	rate of progression, escape, mutation acquisition

Notes

To correlate evolving HIV-1 populations with HLA-A2 restricted immune responses for epitopes in Gag, Pol, Env and Nef, 11 treatment-naive subjects were longitudinally studied. Results show that increased viral load is often associated with broad CTL responses early in infection that persist as an "immunological footprint". Conversely, early, restricted responses may help limit viral load. Phylogenetic and functional evidence of viral escape is seen in Gag, Nef and Pol. Gag and Nef show flanking epitope changes restricted by non-HLA-A2 alleles. As far as modes of viral adaptation, CTL responses were seen to develop both against static viral populations resulting in viral evolution to HLA-A2 as well as against existing mutants resulting in reselection of consensus B-like variants. This study reinforces that CTL immune responses detected are not necessarily beneficial to patients, but may be "footprints" from early effective responses that the virus has since escaped.

References

Karlsson2007 Annika C. Karlsson, Astrid K. N. Iversen, Joan M. Chapman, Tulio de Oliviera, Gerald Spotts, Andrew J. McMichael, Miles P. Davenport, Frederick M. Hecht, and Douglas F. Nixon. Sequential Broadening of CTL Responses in Early HIV-1 Infection Is Associated with Viral Escape. PLoS ONE, 2:e225, 2007. PubMed ID: 17311088. Show all entries for this paper.

Displaying record number 58524

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HXB2 Location	Gag(151-159) p24(19-27) DNA(1240..1266)	Gag Epitope Map
Author Location	p24(19-27)
Epitope	`TLNAWVKVV`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Country	Canada
Experimental methods	Other
Keywords	characterizing CD8+ T cells, elite controllers

Notes

Dual color EliSpot testing for IL-2 and IFN-γ was used to determine whether CTL restricted by MHC Class I alleles associated with slow progression to disease, viz. B*57 and B*27, had a more poly-functional profile than other CD8+ cells in a treatment-naive cohort from Montreal. B*57/B*27-restricted CTL producing IL-2 or IFN-γ or IL-2/IFN-γ, were similar in both slow progressors (SP) and progressors. Other non-protective MHC-I-restricted CTL producing both IL-2/IFN-γ, were greater in number in SP than progressors.
Within SP, peptides restricted by both protective and non-protective MHC-I alleles elicited CTL with the same functional profile. For progressors, peptides and epitopes restricted by protective B*57/B*27 alleles stimulated a higher proportion of dual-(IL-2/IFN-γ)secreting CTL.
HLA-A*02-restricted p24 optimal epitope TLNAWVKVV was tested in a dual color EliSpot and was found to elicit CTL that could produce IL-2 and/or IFN-γ.

References

Peretz2011 Yoav Peretz, Olivia Marra, Réjean Thomas, Danielle Legault, Pierre Côté, Mohamed-Rachid Boulassel, Danielle Rouleau, Jean-Pierre Routy, Rafick-Pierre Sékaly, Christos M Tsoukas, Cécile Tremblay, and Nicole F. Bernard. Relative Contribution of HIV-Specific Functional Lymphocyte Subsets Restricted by Protective and Non-Protective HLA Alleles. Viral Immunol, 24(3):189-198, Jun 2011. PubMed ID: 21668360. Show all entries for this paper.

Displaying record number 58756

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HXB2 Location	Gag(151-159) p24(19-27) DNA(1240..1266)	Gag Epitope Map
Author Location	Gag(151-159)
Epitope	`TLNAWVKVV`	Epitope Alignment
Epitope Name	Gag-TV9
Subtype	B
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Country	Australia, Canada, United States
Experimental methods	Chromium-release assay
Keywords	class I down-regulation by Nef

Notes

Factors impacting Nef-mediated immune evasion were studied using 17 epitopes and the kinetics of infected cell clearance. Recognition and clearance of infected presenting cells by Gag-specific CTL is dependent upon the specific epitope it presents as well as virus inoculum (multiplicity of infection, moi), but not on the particular restricting HLA or on any kinetic advantage for early expressed proteins like Rev, Tat and Nef.
HLA-A*02-restricted Gag TV9-specific CTL were not affected by Nef-mediated down-regulation of HLA as they efficiently lysed infected presenting cells.

References

Chen2012 Diana Y. Chen, Arumugam Balamurugan, Hwee L. Ng, William G. Cumberland, and Otto O. Yang. Epitope Targeting and Viral Inoculum Are Determinants of Nef-Mediated Immune Evasion of HIV-1 from Cytotoxic T Lymphocytes. Blood, 120(1):100-111, 5 Jul 2012. PubMed ID: 22613796. Show all entries for this paper.

Displaying record number 60602

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HXB2 Location	Gag(151-159) p24(19-27) DNA(1240..1266)	Gag Epitope Map
Author Location	p24(19-27)
Epitope	`TLNAWVKVV`	Epitope Alignment
Epitope Name	TV-9
Subtype	B, C
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

Subtype-specific substitutions in two HIV Gag regions (fragments F1, amino acids (aa) 5-46, and F2 aa 100-143) result in novel adaptations that affect epitope processing efficiency. Consequent low epitope abundance is associated with weak T cell response and greater immune escape and therefore with disease state. Conversely, epitopes from these regions when restricted by certain rare HLA I alleles, are associated with greater production and resulting CTL response, therefore delayed disease progression.
Most epitopes were found to be processed as precursors with N-terminal extensions beyond the optimal epitope. Only 4 epitopes in this region were associated with delayed progression - HLA-B*5701/03-restricted IW9 (ISPRTLNAW), KF11 (KAFSPEVIPMF), TW10 (TSTLQEQIGW) and HLA-B*2705-restricted KK10 (KRWIILGLNK).
Regardless of ethnic group, white or African, a significant three-way interaction was found between HLA allelic frequency, epitope yield and ethnicity for epitopes of N-terminal fragment F1 (NF1) and C-terminal as well as middle F2 (CF2 and MF2). C-terminal F1 (CF1) epitope yields however, showed a significant difference between ethnic groups. Also, for identical HLA-mediated selection pressure in both Africans and whites, HIV-C had a lower concentration than HIV-B, especially at lower HLA allelic frequencies.
Epitope TLNAWVKVV, TV-9, from fragment F1, restricted by HLA-A*02, had no determined natural processed epitope forms for subtypes B or C.

References

Tenzer2014 Stefan Tenzer, Hayley Crawford, Phillip Pymm, Robert Gifford, Vattipally B. Sreenu, Mirjana Weimershaus, Tulio de Oliveira, Anne Burgevin, Jan Gerstoft, Nadja Akkad, Daniel Lunn, Lars Fugger, John Bell, Hansjörg Schild, Peter van Endert, and Astrid K. N. Iversen. HIV-1 Adaptation to Antigen Processing Results in Population-Level Immune Evasion and Affects Subtype Diversification. Cell Rep., 7(2):448-463, 24 Apr 2014. PubMed ID: 24726370. Show all entries for this paper.

Displaying record number 57650

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HXB2 Location	Gag(151-159) p24(19-27) DNA(1240..1266)	Gag Epitope Map
Author Location
Epitope	`TLNAWVKVV`	Epitope Alignment
		Show epitope variants
Epitope Name	TV9
Species (MHC/HLA)	(A*02:01)
Immunogen	in vitro stimulation or selection
Experimental methods	Flow cytometric T-cell cytokine assay, HLA binding, TCR binding, Tetramer binding
Keywords	binding affinity, immunodominance, TCR usage, mimotopes

Notes

Mimotopes were used to enhance the immunogenicity of a highly conserved subdominant epitope TV9.
Peptide kiNAWiKVV (TV9p6) with the lowest binding affinity to HLA-A*0201 was selected for detailed analysis and was shown to consistently activate cross-reactive and equally functional CTLs as measured by cytotoxicity, cytokine production and suppression of HIV replication in vitro.
There was some clonal overlap of TCRB gene usage between CTLs primed from the same donors with TV9 or TV9p6, but mostly distinct clonotypes were recruited by each peptide antigen.

References

Schaubert2010 Keri L. Schaubert, David A. Price, Janelle R. Salkowitz, Andrew K. Sewell, John Sidney, Tedi E. Asher, Sylvie E. Blondelle, Sharon Adams, Francesco M. Marincola, Aviva Joseph, Alessandro Sette, Daniel C. Douek, Velpandi Ayyavoo, Walter Storkus, Ming-Ying Leung, Hwee L. Ng, Otto O. Yang, Harris Goldstein, Darcy B. Wilson, and June Kan-Mitchell. Generation of Robust CD8+ T-Cell Responses Against Subdominant Epitopes in Conserved Regions of HIV-1 by Repertoire Mining with Mimotopes. Eur. J. Immunol., 40(7):1950-1962, Jul 2010. PubMed ID: 20432235. Show all entries for this paper.

Displaying record number 55352

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HXB2 Location	Gag(151-159) p24(19-27) DNA(1240..1266)	Gag Epitope Map
Author Location	( LAI)
Epitope	`TLNAWVKVV`	Epitope Alignment
Epitope Name	T9V
Subtype	B
Species (MHC/HLA)	human, transgenic mouse(A*02:01)
Immunogen	HIV-1 infection, vaccine
Country	France
Experimental methods	CD4 T-cell Elispot - IFNγ, Chromium-release assay, Other, Proliferation
Keywords	computational epitope prediction, Th1

Vaccine Details

Vaccine type	protein
Vaccine strain	B clade
Vaccine component	p24 Gag
Adjuvant	Other

Notes

HLA class I/II-transgenic, H-2 class I/II knockout mice, previously used to characterize responses to Hepatitis B vaccine, were used in this study to analyze the HLA-DR1-restricted HIV-1 Gag epitopes.
Peptides were selected with the TEPITOPE algorithm. Of 9 selected peptides 7 were previously reported epitopes and 2 (LLVQNANPDCKTILKALGPA, KTILKALGPAATLEEMMTAC) were novel.
Human relevance of the 2 novel epitopes was established by assaying PBMC from HIV-1-infected long term asymptomatic subjects. KTILKALGPAATLEEMMTA primed CD4+ cells from 2 HLA-DR1 seronegative donors in vitro.
Th1 helper potential was demonstrated for 7 structurally conserved epitopes and was particularly strong with YKTLRAEQASQEVKNWMTET, LLVQNANPDCKTILKALGPA, NKIVRMYSPTSILDIRQGPK.
Epitope T9V was one of 2 CTL reporter epitopes in recombinant mouse invariant chain constructs used for readout in a penatmer staining assay.

References

Pajot2007 Anthony Pajot, Aurélie Schnuriger, Arnaud Moris, Audrey Rodallec, David M. Ojcius, Brigitte Autran, François A. Lemonnier, and Yu-Chun Lone. The Th1 Immune Response against HIV-1 Gag p24-Derived Peptides in Mice Expressing HLA-A02.01 and HLA-DR1. Eur. J. Immunol., 37(9):2635-2644, Sep 2007. PubMed ID: 17668896. Show all entries for this paper.

Displaying record number 59244

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HXB2 Location	Gag(151-159) p24(19-27) DNA(1240..1266)	Gag Epitope Map
Author Location	p24(19-27)
Epitope	`TLNAWVKVV`	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.
TLNAWVKVV was 1 of 7 epitopes with a positive correlation between predicted and observed MHC affinity. TLNAWVKVV had a pattern of transient changes in the dominance of variants, with the founder variant eventually being more dominant.

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 55359

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HXB2 Location	Gag(151-159) p24(19-27) DNA(1240..1266)	Gag Epitope Map
Author Location	p24(19-27)
Epitope	`TLNAWVKVV`	Epitope Alignment
Epitope Name	TV9
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.
Well-defined HLA-A2 restricted epitope TV9, TLNAWVKVV, though infrequently targeted in natural HIV infection is conserved across clades and has one known variant, 9I (TLNAWVKVi). Most people are capable of mounting responses to TV9 with large numbers of CTL.
TV9 affinity for HLA-A*0201 is similar to the relative HLA-A2-binding of Gag epitope SL9, SLYNTVATL. TV9-specific CTLs, however, bound tetramers with a broad range of intensities, indicating structurally diverse clonotypes with heterogeneous avidity to TV9.
TV9, (TLNAWVKVV), is also a part of oligopeptide PRTLNAWVKVVEEKAP where CTL reaction to TV9 was confirmed in one of 2 HLA-A2+, HLA-B*1503-samples (since this peptide contains an HLA-B*1503-restricted epitope as well).

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 152

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HXB2 Location	Gag(151-159) p24(19-27) DNA(1240..1266)	Gag Epitope Map
Author Location	p24( subtype B)
Epitope	`TLNAWVKVV`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A*02:02, A2)
Immunogen	HIV-1 exposed seronegative
Experimental methods
Keywords	subtype comparisons

Notes

HIV-specific CTL were found in exposed seronegative prostitutes from Nairobi -- these CTL may confer protection.
Seroprevalence in this cohort is 90-95% and their HIV-1 exposure is among the highest in the world.
Most isolated HIV strains are clade A in Nairobi, although clades C and D are also found -- B clade epitopes are often cross-reactive, however stronger responses are frequently observed using A or D clade versions of epitopes.
This epitope is conserved among A, B and D clade viruses.
Database note: First author "Rowland-Jones" is also found as "RowlandJones" on annotated papers in this database.

References

Rowland-Jones1998 S. L. Rowland-Jones, T. Dong, K. R. Fowke, J. Kimani, P. Krausa, H. Newell, T. Blanchard, K. Ariyoshi, J. Oyugi, E. Ngugi, J. Bwayo, K. S. MacDonald, A. J. McMichael, and F. A. Plummer. Cytotoxic T cell responses to multiple conserved HIV epitopes in HIV-resistant prostitutes in Nairobi. J. Clin. Invest., 102(9):1758-65, 1 Nov 1998. PubMed ID: 9802890. Show all entries for this paper.

Displaying record number 53399

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HXB2 Location	Gag(151-159) p24(19-27) DNA(1240..1266)	Gag Epitope Map
Author Location	p24( A02, A30, B4402, B15)
Epitope	`TLNAWVKVV`	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 exposed seronegative
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining
Keywords	HIV exposed persistently seronegative (HEPS), characterizing CD8+ T cells

Notes

HIV-specific T-cell response was tested in patients exposed to blood from a patient with highly replicating HIV; these patients were nosocomially infected with HBV, but uninfected with HIV. HIV-specific T-cell responses were directed to structural and non-structural HIV proteins in 2 patients, suggesting that the virus replicated in these patients sufficiently to prime a cell-mediated immune response that protected them from HIV infection.
This patient responded to 4/8 HIV epitopes tested in an IFNgamma EliSpot assay or tetramer assay. Responses were detected to this peptide 8 and 28 weeks after exposure with EliSpot, but not by tetramer binding.

References

Missale2004 Gabriele Missale, Laura Papagno, Amalia Penna, Massimo Pilli, Alessandro Zerbini, Piero Vitali, Giovanni Pieroni, Simona Urbani, Jacopo Uggeri, Susana Pinheiro, Sarah Rowland-Jones, and Carlo Ferrari. Parenteral Exposure to High HIV Viremia Leads to Virus-Specific T Cell Priming without Evidence of Infection. Eur. J. Immunol., 34(11):3208-3215, Nov 2004. PubMed ID: 15459901. Show all entries for this paper.

Displaying record number 56141

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HXB2 Location	Gag(151-159) p24(19-27) DNA(1240..1266)	Gag Epitope Map
Author Location	p24(19-27)
Epitope	`TLNAWVKVV`	Epitope Alignment
		Show epitope variants
Epitope Name	TV9
Subtype	B
Species (MHC/HLA)	human, transgenic mouse(A2)
Immunogen	in vitro stimulation or selection, vaccine
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay
Keywords	variant cross-reactivity

Vaccine Details

Vaccine type	peptide
Adjuvant	Incomplete Freund's Adjuvant (IFA)

Notes

To identify immunogenically optimized peptide epitopes for use in vaccines, two strategies were used. The first studied rare mutant epitopes that were effective in generating a cross-reactive immune response against a range of mutants. The second method was to use a synthetic combinatorial library of peptides and screen for highly effective responses against one epitope (TV9, TLNAWVKVV) and its mutants. Candidate epitopes were tested in HLA-A2 transgenic mice as well as ex vivo human lymphocytes.
Natural TV9 mutants tested in transgenic HLA-A*02 mice showed the following responses - the common mutant V9I, TLNAWVKVi was less immunogenic and had low cross-reactivity. TLNAWVKaV (most cross-reactive) and TLNAWVKai were highly immunogenic and cross-reactive to the consensus. Other rare mutants were TfNAWVKVV, TLNAWVKVl, TLNArVKVV, TLNAWiKVi, TsNAWVKVi and TLNAWVKcV.
Synthetic library mimics chosen were TvNAWnKdV, TLNAWwyaV, TLNAWnKaV, TLNAWnyaV (most immunogenic), TLNAWwydV, TvNAWnyaV, TvNAWwyaV, TvsAvwydV, TLNAWnydV, TLsAWnyaV, TLNAWwKaV, TLsAvwKaV, TLsAWwyaV, TLsAWnydV, TvNAWwKdV and TLNAvwKaV.

References

Blondelle2008 Sylvie E. Blondelle, Rosa Moya-Castro, Keiko Osawa, Kim Schroder, and Darcy B. Wilson. Immunogenically Optimized Peptides Derived from Natural Mutants of HIV CTL Epitopes and Peptide Combinatorial Libraries. Biopolymers, 90(5):683-694, 2008. PubMed ID: 18481808. Show all entries for this paper.

Displaying record number 56726

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HXB2 Location	Gag(151-159) p24(19-27) DNA(1240..1266)	Gag Epitope Map
Author Location
Epitope	`TLNAWVKVV`	Epitope Alignment
Epitope Name	TV9
Species (MHC/HLA)	transgenic mouse(A2)
Immunogen	vaccine
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	escape, variant cross-reactivity, vaccine antigen design

Vaccine Details

Vaccine type	peptide, polyepitope

Notes

The immunogenicity of 3 well-documented A2 epitopes, Gag-TV9, Gag-SL9, and RT-IV9 and their mutants were studied in mice. The conservative mutants (both common and rare) were similar to or less immunogenic than the wild type, while the rare non-conservative mutants were highly immunogenic. Cross-recognition of mutants was highest among mutants occurring at potential TCR contact positions. The authors advocate multi-variant epitope-based vaccine strategies.
One common and 2 rare variants to TV9 were tested. The rare variant TLNAWVKaV was highly immunogenic. The common variants TLNAWVKVi and TLNAWVKVl were weakly immunogenic.
TLNAWVKaV cross reacted with the original epitope TV9.

References

Blondelle2009 Sylvie E. Blondelle, Rosa Moya, Kim Schroder, Keiko Osawa, and Darcy B. Wilson. Natural Mutants of HIV CTL Epitopes with Enhanced Immunogenicity as Potential Vaccine Candidates. Adv. Exp. Med. Biol., 611:379-382, 2009. PubMed ID: 19400233. Show all entries for this paper.

Displaying record number 151

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HXB2 Location	Gag(151-159) p24(19-27) DNA(1240..1266)	Gag Epitope Map
Author Location	p24(151-159)
Epitope	`TLNAWVKVV`	Epitope Alignment
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods
Keywords

Notes

Study of sequence motifs preferred for peptide binding to class I HLA-A2.

References

Parker1992 K. C. Parker, M. A. Bednarek, L. K. Hull, U. Utz, B. Cunningham H. J. Zweerink, W. E. Biddison, and J. E. Coligan. Sequence Motifs Important for Peptide Binding to the Human MHC Class I Molecule, HLA-A2. J. Immunol., 149, 1992. PubMed ID: 1331239. Show all entries for this paper.

Parker1994 K. C. Parker, M. A. Bednarek, and J. E. Coligan. Scheme for Ranking Potential HLA-A2 Binding Peptides Based on Independent Binding of Individual Peptide Side-Chains. J. Immunol., 152, 1994. The authors conclude that peptide amino acid side-chain binding to the HLA-A2 molecule is independent of the sequence of the peptide, and developed a table of coefficients that can be used to help predict peptide binding to HLA-A2. PubMed ID: 8254189. Show all entries for this paper.

Displaying record number 1439

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HXB2 Location	Gag(151-159) p24(19-27) DNA(1240..1266)	Gag Epitope Map
Author Location	p24(19-27)
Epitope	`TLNAWVKVV`	Epitope Alignment
Species (MHC/HLA)	human(A2)
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 60503

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HXB2 Location	Gag(151-159) p24(19-27) DNA(1240..1266)	Gag Epitope Map
Author Location	p24
Epitope	`TLNAWVKVV`	Epitope Alignment
Subtype	B, C, CRF01_AE
Species (MHC/HLA)	human
Immunogen	in vitro stimulation or selection
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	epitope processing

Notes

Proteasomal degradation and epitope processing were compared in vitro for Gag-p24 epitopes from 3 subtypes of HIV-1: B, C, CRF01_AE as a function of epitope flanking regions. Synthetic flanking regions were chosen to flank epitopes of study based on highest and lowest frequencies of amino acids (aa) related to proteasomal cleavage sites. Effective processing, presentation and IFN-γ production was best for peptides containing flanking regions designed to promote epitope generation. Most epitopes generated were cleaved immediately after the C-terminal aa of that epitope.
No significant difference was seen between subtypes in peptide number generated, but differences were seen in sequence within or flanking the epitope.
Proteasome target fragment-3 (PTF-3) peptide, {MSIQMLAQVIKE}TLNAWVKVV{KILMFKLNAPA}, contained the epitope TLNAWVKVV and optimal epitope generation flanking regions. It generated fragments {VIKE}TLNAWVKVV{KILMFKLN}, {KE}TLNAWVKVV, TLNAWVKVV{KI}, NAWVKVV in addition to the epitope. Other synthetic peptides used were PTF-3F, {AEQIGWEFDDFF}TNLAWVKVV{FDCFCRQGPKE} for limited epitope generation that did not generate any processed epitope or fragments; as well as PTF-3N {IQGQMVHQAISPR}TNLAWVKVV{EEKAFSPEVIPM}, the natural sequence, which generated fragments {SPR}TNLAWVKVV, {R}TNLAWVKVV and NAWVKVV in addition to the epitope, TNLAWVKVV.

References

Steers2014 Nicholas J. Steers, Jeffrey R. Currier, Ousman Jobe, Sodsai Tovanabutra, Silvia Ratto-Kim, Mary A. Marovich, Jerome H. Kim, Nelson L. Michael, Carl R. Alving, and Mangala Rao. Designing the Epitope Flanking Regions for Optimal Generation of CTL Epitopes. Vaccine, 32(28):3509-3516, 12 Jun 2014. PubMed ID: 24795226. Show all entries for this paper.