Search CTL/CD8+ T-Cell Epitope Database

Found 23 matching records:

Displaying record number 1984

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HXB2 Location	Gag(362-370) p24(230)-p2p7p1p6(7) DNA(1873..1899)	Gag Epitope Map
Author Location	p24
Epitope	`VLAEAMSQV`	Epitope Alignment
Epitope Name	Gag-VV9; p24-VV9
Subtype	B
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	HAART, ART

Notes

Among HIV+ individuals who carried HLA A*02, 3/29 (10%) recognized this epitope.

References

Sabbaj2003 Steffanie Sabbaj, Anju Bansal, G. Douglas Ritter, Christopher Perkins, Bradley H. Edwards, Ethan Gough, Jianming Tang, James J. Szinger, Bette Korber, Craig M. Wilson, Richard A. Kaslow, Mark J. Mulligan, and Paul A. Goepfert. Cross-Reactive CD8+ T Cell Epitopes Identified in US Adolescent Minorities. J. Acquir. Immune Defic. Syndr., 33(4):426-438, 1 Aug 2003. PubMed ID: 12869831. Show all entries for this paper.

Displaying record number 54558

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HXB2 Location	Gag(362-370) p24(230)-p2p7p1p6(7) DNA(1873..1899)	Gag Epitope Map
Author Location	Gag(363-370)
Epitope	`VLAEAMSQV`	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 60377

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HXB2 Location	Gag(362-370) p24(230)-p2p7p1p6(7) DNA(1873..1899)	Gag Epitope Map
Author Location	Gag(362-370)
Epitope	`VLAEAMSQV`	Epitope Alignment
Epitope Name	VV9
Species (MHC/HLA)	human(A*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.
VLAEAMSQV had a significantly positive association with HLA A*02; it was recognized by 15/134 A*02-positive subjects and 6/190 A*02-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 53843

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HXB2 Location	Gag(362-370) p24(230)-p2p7p1p6(7) DNA(1873..1899)	Gag Epitope Map
Author Location	p24-p2p7p1p6(362-370)
Epitope	`VLAEAMSQV`	Epitope Alignment
		Show epitope variants
Epitope Name	VV9
Species (MHC/HLA)	human(A*02)
Immunogen	HIV-1 infection
Patient MHC/HLA	M-1005: A02, A32, B07, B40, C03, C07; P-1026: A24, A32, B07, B18, C*07
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	responses in children, mother-to-infant transmission, escape, acute/early infection, viral fitness and reversion

Notes

CD8 T-cell responses were examined in mother-infant pairs. Escape variants were commonly detected in maternal plasma. Early infant plasma viruses showed heterogeneity of gag and nef gene sequences as well as mother-to-child transmission of CD8 T-cell escape variants. The stability of escape mutants in the infant over time was determined by infant HLA haplotype and viral fitness.
Sequential plasma specimens from infants showed changes in CD8 T-cell epitope sequences, suggesting that infants are capable of generating virus-specific CD8 T-cell responses.
The mother (M-1005) was A02+ and carried a variant form of the epitope, VLAEAMShV, which she passed to her A02- child (P-1026). This form persisted in her child for 15 months.

References

Sanchez-Merino2005 Victor Sanchez-Merino, Siwei Nie, and Katherine Luzuriaga. HIV-1-Specific CD8+ T Cell Responses and Viral Evolution in Women and Infants. J. Immunol., 175(10):6976-6986, 15 Nov 2005. PubMed ID: 16272358. Show all entries for this paper.

Displaying record number 1305

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HXB2 Location	Gag(362-370) p24(230)-p2p7p1p6(7) DNA(1873..1899)	Gag Epitope Map
Author Location	Gag(386-)
Epitope	`VLAEAMSQV`	Epitope Alignment
Epitope Name	Gag-386
Species (MHC/HLA)	human(A*02:01)
Immunogen	HIV-1 infection
Experimental methods
Keywords	binding affinity, supertype, computational epitope prediction, immunodominance, HLA cross-presentation

Notes

HIV was scanned for all peptides which carried the A2-supermotif pattern conserved in more than 50% of B clade sequences -- 233 peptides met this criteria, and 30 of these bound to HLA-A*0201 -- 20/30 bound to at least 3/5 of HLA-A2 supertype alleles tested.
Three additional previously described HLA-A2 epitopes were added to the set of 20, and 18/22 chronically infected HLA-A2 individuals had CTL that recognized at least one of the 23 peptides (median of 2 and maximum of 6), while 6/12 acute infected individuals recognized at least 1 (median of 1 and maximum of 2)
VLAEAMSQV binds to all five HLA-A2 supertype alleles tested: A*0201, A*0202, A*0203, A*0206 and A*6802 (highest affinity)
4/22 individuals with chronic HIV-1 infection recognized this epitope, and it was immunodominant in 3/4 by ELISPOT.
0/12 acutely infected individuals recognized this epitope.

References

Altfeld2001 M. A. Altfeld, B. Livingston, N. Reshamwala, P. T. Nguyen, M. M. Addo, A. Shea, M. Newman, J. Fikes, J. Sidney, P. Wentworth, R. Chesnut, R. L. Eldridge, E. S. Rosenberg, G. K. Robbins, C. Brander, P. E. Sax, S. Boswell, T. Flynn, S. Buchbinder, P. J. Goulder, B. D. Walker, A. Sette, and S. A. Kalams. Identification of novel HLA-A2-restricted human immunodeficiency virus type 1-specific cytotoxic T-lymphocyte epitopes predicted by the HLA-A2 supertype peptide-binding motif. J. Virol., 75(3):1301-11, Feb 2001. URL: http://jvi.asm.org/cgi/content/full/75/3/1301. PubMed ID: 11152503. Show all entries for this paper.

Displaying record number 53071

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HXB2 Location	Gag(362-370) p24(230)-p2p7p1p6(7) DNA(1873..1899)	Gag Epitope Map
Author Location	Gag
Epitope	`VLAEAMSQV`	Epitope Alignment
		Show epitope variants
Epitope Name	Gag 386
Subtype	M group
Species (MHC/HLA)	human, humanized mouse, mouse(A*02:01)
Immunogen	in vitro stimulation or selection, vaccine
Experimental methods	Cytokine production, T-cell Elispot
Keywords	subtype comparisons, computational epitope prediction, escape, TCR usage, variant cross-reactivity

Vaccine Details

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

Notes

This study examined variant recognition of epitopes presented by A*0201 and A*1101. Numerous amino acid substitutions can be introduced into epitopes without disrupting their recognition by CTLs, although epitopes with multiple substitutions were less recognized. An algorithm was constructed for prediction of epitopes capable of inducing responses to a great number of variant epitopes.
A total of 20 variant forms of Gag 386 were identified. More than 95% of the variant epitopes were recognized by CTLs from mice immunized with the parental form.
Gag 386 epitope ( parent or variant form) was present in 97% of HIV sequences of many M group subtypes.

References

McKinney2004 Denise M. McKinney, Rhonda Skvoretz, Brian D. Livingston, Cara C. Wilson, Michelle Anders, Robert W. Chesnut, Alessandro Sette, Max Essex, Vladimir Novitsky, and Mark J. Newman. Recognition of Variant HIV-1 Epitopes from Diverse Viral Subtypes by Vaccine-Induced CTL. J. Immunol., 173(3):1941-1950, 1 Aug 2004. PubMed ID: 15265928. Show all entries for this paper.

Displaying record number 56186

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HXB2 Location	Gag(362-370) p24(230)-p2p7p1p6(7) DNA(1873..1899)	Gag Epitope Map
Author Location	Gag(386-)
Epitope	`VLAEAMSQV`	Epitope Alignment
Species (MHC/HLA)	human(A*02:01)
Immunogen	vaccine
Country	Botswana, United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay
Keywords	vaccine antigen design

Vaccine Details

Vaccine type	DNA, polyepitope
Vaccine strain	multiple epitope immunogen

Notes

This is a trial of a multi-epitope DNA vaccine that included 21 CTL epitopes, which are conserved among clades A,B,C,D and CRFs and are supertype binding peptides of A1, A3 and B7 supertypes. Participants were from US and Botswana.
The vaccine was safe and well-tolerated, but the rate of CTL induction was low. CD8+ responses (and no CD4+ responses) were detected in 3/26 subjects using chromium release assay and in 2/42 subjects using IFN-γ ELISPOT assay.
This epitope was included in the vaccine.

References

Gorse2008a Geoffrey J. Gorse, Lindsey R. Baden, Margaret Wecker, Mark J. Newman, Guido Ferrari, Kent J. Weinhold, Brian D. Livingston, Tonya L. Villafana, Hongli Li, Elizabeth Noonan, Nina D. Russell, and HIV Vaccine Trials Network. Safety and Immunogenicity of Cytotoxic T-Lymphocyte Poly-Epitope, DNA Plasmid (EP HIV-1090) Vaccine in Healthy, Human Immunodeficiency Virus Type 1 (HIV-1)-Uninfected Adults. Vaccine, 26(2):215-223, 10 Jan 2008. PubMed ID: 18055072. Show all entries for this paper.

Displaying record number 56527

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HXB2 Location	Gag(362-370) p24(230)-p2p7p1p6(7) DNA(1873..1899)	Gag Epitope Map
Author Location	Gag
Epitope	`VLAEAMSQV`	Epitope Alignment
Epitope Name	Gag386
Subtype	B
Species (MHC/HLA)	human(A2)
Immunogen	vaccine
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	vaccine antigen design

Vaccine Details

Vaccine type	DNA, polyepitope
Vaccine component	other

Notes

DNA vaccine EP HIV-1090 evaluation in patients receiving ART was done. This vaccine is composed of multiple CTL epitopes, all associated with certain HLA supertypes. Differences of CTL response rate in vaccine and placebo recipients however, was not significant.
VLAEAMSQV is a Gag epitope encoded in the EP HIV-1090 polyepitope vaccine.

References

Wilson2008 Cara C. Wilson, Mark J. Newman, Brian D. Livingston, Samantha MaWhinney, Jeri E. Forster, Jim Scott, Robert T. Schooley, and Constance A. Benson. Clinical Phase 1 Testing of the Safety and Immunogenicity of an Epitope-Based DNA Vaccine in Human Immunodeficiency Virus Type 1-Infected Subjects Receiving Highly Active Antiretroviral Therapy. Clin. Vaccine Immunol., 15(6):986-994, Jun 2008. PubMed ID: 18400976. Show all entries for this paper.

Displaying record number 52666

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HXB2 Location	Gag(362-370) p24(230)-p2p7p1p6(7) DNA(1873..1899)	Gag Epitope Map
Author Location	Gag(362-)
Epitope	`VLAEAMSQV`	Epitope Alignment
		Show epitope variants
Epitope Name	Gag362(9L)
Species (MHC/HLA)	human, transgenic mouse(A2)
Immunogen	HIV-1 infection, vaccine
Experimental methods	Chromium-release assay, Flow cytometric T-cell cytokine assay, T-cell Elispot
Keywords	binding affinity, subtype comparisons, computational epitope prediction

Vaccine Details

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

Notes

HLA-A2-restricted HIV-1 CTL epitopes were computationally predicted. Binding affinities for HLA-A*0204, immunogenicity in HLA-A*0201 transgenic mice, and responses to the peptides in 17 HIV-1 infected patients were tested. 31 novel conserved A2 epitopes were detected. An average of 4 epitopes were recognized per patient.
This peptide was a good A2 binder that induced CTL and CD8+ T-cell IFN gamma responses in mice. Responses were detected in 1/17 HIV+ HLA-A2 subjects.
The variant vlaeamsqA was also immunogenic in A2 transgenic mice, eliciting a CD8+ T-cell response, as was recognized in 3/17 HIV+ people, including the person that recognized the vlaeamsqV variant.

References

Corbet2003 Sylvie Corbet, Henrik Vedel Nielsen, Lasse Vinner, Sanne Lauemoller, Dominic Therrien, Sheila Tang, Gitte Kronborg, Lars Mathiesen, Paul Chaplin, Søren Brunak, Søren Buus, and Anders Fomsgaard. Optimization and Immune Recognition of Multiple Novel Conserved HLA-A2, Human Immunodeficiency Virus Type 1-Specific CTL Epitopes. J. Gen. Virol., 84(Pt 9):2409-2421, Sep 2003. PubMed ID: 12917462. Show all entries for this paper.

Displaying record number 53582

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HXB2 Location	Gag(362-370) p24(230)-p2p7p1p6(7) DNA(1873..1899)	Gag Epitope Map
Author Location	p24(230-238)
Epitope	`VLAEAMSQV`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, HLA binding
Keywords	acute/early infection, optimal epitope

Notes

The most frequently targeted HLA-A*02-restricted CD8+ T-cell epitopes in chronic infection were significantly less frequently recognized during primary infection. This epitope was only recognized during chronic infection.

References

Altfeld2005a Marcus Altfeld, Todd M. Allen, Elizabeth T. Kalife, Nicole Frahm, Marylyn M. Addo, Bianca R. Mothe, Almas Rathod, Laura L. Reyor, Jason Harlow, Xu G. Yu, Beth Perkins, Loren K. Robinson, John Sidney, Galit Alter, Mathias Lichterfeld, Alessandro Sette, Eric S. Rosenberg, Philip J. R. Goulder, Christian Brander, and Bruce D. Walker. The Majority of Currently Circulating Human Immunodeficiency Virus Type 1 Clade B Viruses Fail To Prime Cytotoxic T-Lymphocyte Responses against an Otherwise Immunodominant HLA-A2-Restricted Epitope: Implications for Vaccine Design. J. Virol., 79(8):5000-5005, Apr 2005. PubMed ID: 15795285. Show all entries for this paper.

Displaying record number 54233

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HXB2 Location	Gag(362-370) p24(230)-p2p7p1p6(7) DNA(1873..1899)	Gag Epitope Map
Author Location	p24
Epitope	`VLAEAMSQV`	Epitope Alignment
Epitope Name	A2-VV9(gp24)
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	rate of progression, immunodominance, early-expressed proteins

Notes

Immunodominant HIV epitopes in early, primary infection of CTLs were identified and the relative contributions of immune responses restricted to individual HLA class I molecules were studied.
This epitope-HLA combination was recognized. The most frequently recognized epitopes also elicited the greatest CTL response.
HIV-1 Epitope sequence variability was not correlated with immunodominant versus immune sub-dominant responses.
HLA-B*57 and HLA-B*27 restricted responses were the strongest in these early and acute infections - due to dominant responses to a single epitope in each case (TW10 for B*57 and KK10 for B*27).
In the presence of HLA-B*57 and HLA-B*27 restricted responses, the relative contributions of other restricting HLA dropped greatly.

References

Altfeld2006 Marcus Altfeld, Elizabeth T. Kalife, Ying Qi, Hendrik Streeck, Mathias Lichterfeld, Mary N. Johnston, Nicole Burgett, Martha E. Swartz, Amy Yang, Galit Alter, Xu G. Yu, Angela Meier, Juergen K. Rockstroh, Todd M. Allen, Heiko Jessen, Eric S. Rosenberg, Mary Carrington, and Bruce D. Walker. HLA Alleles Associated with Delayed Progression to AIDS Contribute Strongly to the Initial CD8+ T Cell Response against HIV-1. PLoS Med., 3(10):e403, Oct 2006. PubMed ID: 17076553. Show all entries for this paper.

Displaying record number 54855

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HXB2 Location	Gag(362-370) p24(230)-p2p7p1p6(7) DNA(1873..1899)	Gag Epitope Map
Author Location	p2p7p1p6(362-370 Henan isolate)
Epitope	`VLAEAMSQV`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Country	China
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords

Notes

CTL responses were studied in treated and untreated donors from China, using Gag peptides from Henan isolate. All peptides were predicted to have A2 or A11 restriction (two of the most prominent alleles in Chinese population) and HLA restriction was further analyzed by CTL recognition in patients carrying corresponding allele. Among treated donors, HLA-A2 donors had higher CTL response than than HLA-A11 donors. Chronically infected untreated individuals had higher magnitude of CTL response than treated ones.
While VLAEAMSQV was described previously to have strong CTL response in HLA-A2 individuals, in this study 8 of 13 (61%) A2-positive individuals demonstrated moderate response to this peptide.

References

Gong2006 Xiaoyan Gong, Xien Gui, Yuxia Zhang, and Po Tien. Screening for CD8 Cytotoxic T Lymphocytes Specific for Gag of Human Immunodeficiency Virus Type 1 Subtype B' Henan Isolate from China and Identification of Novel Epitopes Restricted by the HLA-A2 and HLA-A11 Alleles. J. Gen. Virol., 87(Pt 1):151-158, Jan 2006. PubMed ID: 16361427. Show all entries for this paper.

Displaying record number 55371

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HXB2 Location	Gag(362-370) p24(230)-p2p7p1p6(7) DNA(1873..1899)	Gag Epitope Map
Author Location
Epitope	`VLAEAMSQV`	Epitope Alignment
		Show epitope variants
Epitope Name	Gag 362(9V)
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Country	Denmark
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, Flow cytometric T-cell cytokine assay, Intracellular cytokine staining
Keywords	variant cross-reactivity

Notes

11 HLA-A2+ (A*0201, A*0220, A*0234 or A*0236), patients' HIV were sequenced. Of 28 epitopes studied, most were conserved and elicited a subdominant CTL response. 9 epitopes in 7 proteins showed T-cell cross reaction. These epitopes were optimized to induce more immunogenic but cross-reacting responses.
Epitopes in Gag, Pol, Env, Nef were more conserved than epitopes in shorter proteins Vpu, Vif, Vpr and Rev. Most natural epitopes were untargeted or targeted by 1 or 2 patients.
Gag 362(9V) VLAEAMSQV epitope was found in 8 patients but only 1 had a CTL immune response to it.
A variant, 9A (VLAEAMSQa) involving the C-terminal anchor binding position was cross-recognized by CTLs to this epitope.

References

Thorn2007 Mette Thorn, Sheila Tang, Dominic Therrien, Henrik Kløverpris, Lasse Vinner, Gitte Kronborg, Jan Gerstoft, Sylvie Corbet, and Anders Fomsgaard. Sequence Conservation of Subdominant HLA-A2-Binding CTL Epitopes in HIV-1 Clinical Isolates and CD8+ T-Lymphocyte Cross-Recognition May Explain the Immune Reaction in Infected Individuals. APMIS, 115(6):757-768, Jun 2007. PubMed ID: 17550385. Show all entries for this paper.

Displaying record number 56059

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HXB2 Location	Gag(362-370) p24(230)-p2p7p1p6(7) DNA(1873..1899)	Gag Epitope Map
Author Location	Gag(362-)
Epitope	`VLAEAMSQV`	Epitope Alignment
		Show epitope variants
Epitope Name	Gag362(9V)
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Country	Denmark
Experimental methods	Flow cytometric T-cell cytokine assay
Keywords	rate of progression, escape, acute/early infection

Notes

Comparative genetic and immunological study was conducted of two subjects - patient DK1 with no viremia for >10 years after transient ART and despite continued sexual contact with patient UG1 (his wife) who was an HIV-1-positive non-controller.
DK1 and UG1 shared most crossover points of recombination but while DK1 had subtype A1 Env, UG1's Env was subtype D. In the shared subtype A1/D regions, homology between the patients' sequences was 98%.
Out of 23 conserved HLA-A02 epitopes, HLA-A2+ DK1 produced CTL response and IFN-gamma response only to epitope ILKEPVHGV.
DK1 produced neutralizing antibody only to homologous isolates. It is suggested that early, transient ART may have resulted in full control of viremia and disease via the very narrow specific CTL response and neutralizing antibody.
Despite carrying HLA-A2, DK1 did not respond to HLA-A2 Gag epitope VLAEAMSQV, though it did elicit response in a cohort of 11 other HIV-1+ HLA-A2+ patients. A variant of this epitope, VLAEAMSQa, was seen in DK1.

References

Fomsgaard2008 Anders Fomsgaard, Lasse Vinner, Dominic Therrien, Louise B. Jørgensen, Claus Nielsen, Lars Mathiesen, Court Pedersen, and Sylvie Corbet. Full-Length Characterization of A1/D Intersubtype Recombinant Genomes from a Therapy-Induced HIV Type 1 Controller during Acute Infection and His Noncontrolling Partner. AIDS Res. Hum. Retroviruses, 24(3):463-472, Mar 2008. PubMed ID: 18373434. Show all entries for this paper.

Displaying record number 60376

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HXB2 Location	Gag(362-370) p24(230)-p2p7p1p6(7) DNA(1873..1899)	Gag Epitope Map
Author Location	Gag(362-370)
Epitope	`VLAEAMSQV`	Epitope Alignment
Epitope Name	VV9
Species (MHC/HLA)	human(A*29)
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.
VLAEAMSQV had a significantly positive association with HLA A*29; it was recognized by 4/20 A*29-positive subjects and 2/170 A*29-negative subjects.

References

Displaying record number 55741

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HXB2 Location	Gag(362-370) p24(230)-p2p7p1p6(7) DNA(1873..1899)	Gag Epitope Map
Author Location	Gag
Epitope	`VLAEAMSQV`	Epitope Alignment
Epitope Name	Gag386
Subtype	A, B, C, D
Species (MHC/HLA)	human, mouse(A2 supertype)
Immunogen	HIV-1 infection
Country	United States
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	binding affinity, supertype, vaccine-induced immune responses, HLA cross-presentation

Notes

21 supertype-A2, -A3 and -B7-restricted epitopes predicted to be immunogenic by HLA-peptide binding motifs and phenotypic frequency in individuals were recognized by HIV-1+ subjects in ELISpot assays and shown to bind with high affinity to minimum 3 HLA-alleles of the restricting supertype. These epitopes were included in DNA vaccine EP HIV-1090 that avoided immunodominant responses and did not restrict subject immunity to predicted HLA-type when tested in mice. Transgenic mice mounted a vaccine-response similar to that induced by ELISpot assay in humans.
Epitope VLAEAMSQV of the HLA-A2 supertype bound most strongly to HLA-A*0203, -A*0201, -A*0202 and -A*0206, but also to -A*6802. It was conserved 100% in subtype A, 74% in B, 13% in C and 25% in subtype D. 2/22 HLA-A2 supertype expressing HIV-1+ subjects mounted a positive ELISpot response to Gag386.

References

Wilson2003 Cara C. Wilson, Denise McKinney, Michelle Anders, Samantha MaWhinney, Jeri Forster, Claire Crimi, Scott Southwood, Alessandro Sette, Robert Chesnut, Mark J Newman, and Brian D Livingston. Development of a DNA Vaccine Designed to Induce Cytotoxic T Lymphocyte Responses to Multiple Conserved Epitopes in HIV-1. J. Immunol., 171(10):5611-5623, 15 Nov 2003. PubMed ID: 14607970. Show all entries for this paper.

Displaying record number 1587

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HXB2 Location	Gag(362-370) p24(230)-p2p7p1p6(7) DNA(1873..1899)	Gag Epitope Map
Author Location	Gag(397-405)
Epitope	`VLAEAMSQV`	Epitope Alignment
Species (MHC/HLA)	human(A2 supertype)
Immunogen	HIV-1 infection
Experimental methods
Keywords	supertype, rate of progression

Notes

Long-term nonprogressors (LTNPs) had strong memory resting CD8+ T-cell responses against the majority of epitopes tested, (18 for the A2 supertype, 16 for the A3 supertype) while the effector cells of long-term nonprogressors recognized far fewer epitopes.
Progressors had memory resting CD8+ T-cells that recognized far fewer epitopes than LTNPs.
A positive correlation between effector CD8+ T-cells and plasma viremia and a negative correlation between CD8+ effector T-cells and CD4+ T-cells was observed, which may contribute to the inability of LTNPs to clear virus.
This epitope can bind all five HLA-A2 supertypes alleles (A*0201, A*0202, A*0203, A*0206 and A*6802)

References

Propato2001 A. Propato, E. Schiaffella, E. Vicenzi, V. Francavilla, L. Baloni, M. Paroli, L. Finocchi, N. Tanigaki, S. Ghezzi, R. Ferrara, R. Chesnut, B. Livingston, A. Sette, R. Paganelli, F. Aiuti, G. Poli, and V. Barnaba. Spreading of HIV-specific CD8+ T-cell repertoire in long-term nonprogressors and its role in the control of viral load and disease activity. Hum. Immunol., 62(6):561-76, Jun 2001. PubMed ID: 11390031. Show all entries for this paper.

Displaying record number 60378

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HXB2 Location	Gag(362-370) p24(230)-p2p7p1p6(7) DNA(1873..1899)	Gag Epitope Map
Author Location	Gag(362-370)
Epitope	`VLAEAMSQV`	Epitope Alignment
Epitope Name	VV9
Species (MHC/HLA)	human(A*69)
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.
VLAEAMSQV had a significantly positive association with HLA A*69; it was recognized by 1/2 A*69-positive subjects and 1/168 A*69-negative subjects.

References

Displaying record number 60375

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HXB2 Location	Gag(362-370) p24(230)-p2p7p1p6(7) DNA(1873..1899)	Gag Epitope Map
Author Location	Gag(362-370)
Epitope	`VLAEAMSQV`	Epitope Alignment
Epitope Name	VV9
Species (MHC/HLA)	human(C*14)
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.
VLAEAMSQV had a significantly positive association with HLA C*14; it was recognized by 7/17 C*14-positive subjects and 21/324 C*14-negative subjects.

References

Displaying record number 60379

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HXB2 Location	Gag(362-370) p24(230)-p2p7p1p6(7) DNA(1873..1899)	Gag Epitope Map
Author Location	Gag(362-370)
Epitope	`VLAEAMSQV`	Epitope Alignment
Epitope Name	VV9
Species (MHC/HLA)	human(C*16)
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.
VLAEAMSQV had a significantly positive association with HLA C*16; it was recognized by 1/7 C*16-positive subjects and 0/161 C*16-negative subjects.

References

Displaying record number 58041

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HXB2 Location	Gag(362-370) p24(230)-p2p7p1p6(7) DNA(1873..1899)	Gag Epitope Map
Author Location	Gag
Epitope	`VLAEAMSQV`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human
Immunogen	vaccine
Patient MHC/HLA	A02:01, A43:01, B40:01, B53:01, C03:04, C04:01
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	vaccine-induced immune responses

Vaccine Details

Vaccine type	adenovirus type 5 (Ad5), DNA prime with Ad5 boost
Vaccine strain	B clade IIIB, B clade JRFL, B clade CAM-1
Vaccine component	Gag, Nef, Pol

Notes

T-cell epitope response specificities were examined in uninfected subjects who received the Gag/Pol/Nef vaccine used in the Step trial. Variable epitopes were detected more frequently than would be expected from an unbiased sampling. The most conserved epitopes were detected at a lower frequency, similar to the frequency reported for responses to natural infection, suggesting potential epitope masking. This may be a mechanism used by the virus in both contexts to escape effective T-cell surveillance. Development of vaccine strategies that can elicit a greater breadth, and towards conserved regions of the genome in particular, are critical requirements for effective T-cell based vaccines.
All vacinees had responses to the Gag peptide pool, and most also had responses to the Nef and/or Pol pools. Subsequent mapping using 9mer minipools demonstrated that T-cell epitopes were recognized across the length of all 3 proteins. A total of 105 distinct 9mers were detected, although some of these may have been overlapping 9mers representing a single epitope.
1 vaccinee recognized 9mer VLAEAMSQV.

References

Li2011a Fusheng Li, Adam C. Finnefrock, Sheri A. Dubey, Bette T. M. Korber, James Szinger, Suzanne Cole, M. Juliana McElrath, John W. Shiver, Danilo R. Casimiro, Lawrence Corey, and Steven G Self. Mapping HIV-1 Vaccine Induced T-Cell Responses: Bias Towards Less-Conserved Regions and Potential Impact on Vaccine Efficacy in the Step Study. PLoS One, 6(6):e20479, 2011. PubMed ID: 21695251. Show all entries for this paper.

Displaying record number 57027

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HXB2 Location	Gag(362-370) p24(230)-p2p7p1p6(7) DNA(1873..1899)	Gag Epitope Map
Author Location	Gag
Epitope	`VLAEAMSQV`	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	Sweden
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	subtype comparisons, computational epitope prediction, vaccine antigen design

Notes

From HIV-1 sequences of multiple subtypes, bioinformatic prediction generated 174 CTL epitopes from Gag, Pol, Nef, Env and Tat restricted by HLA supertypes A1, A2, A3, A24, B7, B44 and B58; 10 previously-published A2- and B58-restricted epitopes were also included. Of these 184 epitopes, 113 were recognized experimentally in serum from 31 HIV+ patients.
While Gag, Pol, Env and Nef were highly immunogenic, only 38% of Tat epitopes elicited a response.
VLAEAMSQV was a predicted epitope restricted by A2 supertype. 1/31 patient(s) responded to it; the patient was known to carry an allele of A2 supertype. Responding patients were infected with HIV clade(s) C.

References

Perez2008 Carina L. Pérez, Mette V. Larsen, Rasmus Gustafsson, Melissa M. Norström, Ann Atlas, Douglas F. Nixon, Morten Nielsen, Ole Lund, and Annika C. Karlsson. Broadly Immunogenic HLA Class I Supertype-Restricted Elite CTL Epitopes Recognized in a Diverse Population Infected with Different HIV-1 Subtypes. J. Immunol., 180(7):5092-5100, 1 Apr 2008. PubMed ID: 18354235. Show all entries for this paper.

Displaying record number 61340

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HXB2 Location	Gag(362-370) p24(230)-p2p7p1p6(7) DNA(1873..1899)	Gag Epitope Map
Author Location	Gag
Epitope	`VLAEAMSQV`	Epitope Alignment
Species (MHC/HLA)	human
Immunogen	vaccine
Country	Australia, Brazil, Canada, Dominican Republic, Haiti, Jamaica, Peru, Puerto Rico, United States
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	vaccine-induced immune responses, assay or method development, optimal epitope

Vaccine Details

Vaccine type	adenovirus type 5 (Ad5)
Vaccine component	Gag, Nef, Pol

Notes

Small pools of 15-mer peptides (7-30) were used to map T-cell epitopes. 2 such methods (mini- and maxi-pool strategies) used up to 7.7x less EliSpot assays than the traditional 'test-all' method of using each peptide-epitope individually. While the test-all method identified the largest number of epitopes and some EliSpots are only positive when shorter, more optimal peptides are used, overall this strategy is best for following vaccine trials and other large epitope-mapping studies.
37 15-mers and 27 optimal peptides representing 13 optimal epitopes gave CTL responses out of the 134 tested.
Optimal epitope VLAEAMSQV elicited response of 201.7 sfc/million PBMC from participants in the Step HIV-1 vaccine efficacy trial who were uninfected at the time of testing. It was part of 15-mers ARVLAEAMSQVTNSA and PGHKARVLAEAMSQV.

References

Fiore-Gartland2016 Andrew Fiore-Gartland, Bryce A. Manso, David P. Friedrich, Erin E. Gabriel, Greg Finak, Zoe Moodie, Tomer Hertz, Stephen C. De Rosa, Nicole Frahm, Peter B. Gilbert, and M Juliana McElrath. Pooled-Peptide Epitope Mapping Strategies Are Efficient and Highly Sensitive: An Evaluation of Methods for Identifying Human T Cell Epitope Specificities in Large-Scale HIV Vaccine Efficacy Trials. PLoS One, 11(2):e0147812, 2016. PubMed ID: 26863315. Show all entries for this paper.