Search CTL/CD8+ T-Cell Epitope Database

Found 11 matching records:

Displaying record number 61153

Download this epitope record as JSON.

HXB2 Location	Gag(341-349) p24(209-217) DNA(1810..1836)	Gag Epitope Map
Author Location
Epitope	`ATLEEMMTA`	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human, mouse(A*02:06)
Immunogen	HIV-1 infection, vaccine
Country	Japan
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	vaccine-induced immune responses, vaccine antigen design

Vaccine Details

Vaccine type	DNA, modified vaccinia Ankara (MVA), adenovirus
Vaccine strain	B clade

Notes

Using 3 strategies, (1) in silico-designed multivalent-mosaic proteins for greater breadth, magnitude, cross-reactivity (2) highly conserved epitopes for loss of replicative fitness and oligofunctional inter-clade specific T-cell production (3) beneficial CTL epitopes associated with low viral load (VL) for broad immune response; a conserved bivalent-mosaic immunogen, tHIV-consvX, was designed and vectored by plasmid DNA, ChAdOx1, and MVA for testing in mice and humans. Strong preclinical immunogenicity was seen in mice and in 120 untreated, chronic HIV-1 patients, tHIVconsvX-specific CTLs correlated with high CD4+ T cell count but not VL.
Env was excluded from this second generation vaccine as its short, conserved stretch has no beneficial epitopes and while its epitopes are immunodominant, they are not associated with good control of viremia.
Protective Japanese epitope ATLEEMMTAL was present in mosaics 1 and 2 of the second generation tHIVconsvX vaccine.

References

Ondondo2016 Beatrice Ondondo, Hayato Murakoshi, Genevieve Clutton, Sultan Abdul-Jawad, Edmund G.-T. Wee, Hiroyuki Gatanaga, Shinichi Oka, Andrew J. McMichael, Masafumi Takiguchi, Bette Korber, and Tomáš Hanke. Novel Conserved-region T-cell Mosaic Vaccine With High Global HIV-1 Coverage Is Recognized by Protective Responses in Untreated Infection. Mol. Ther., 24(4):832-842, Apr 2016. PubMed ID: 26743582. Show all entries for this paper.

Displaying record number 61507

Download this epitope record as JSON.

HXB2 Location	Gag(341-349) p24(209-217) DNA(1810..1836)	Gag Epitope Map
Author Location	Gag(341-349)
Epitope	`ATLEEMMTA`	Epitope Alignment
Epitope Name	GagAA9
Subtype	B
Species (MHC/HLA)	human(A*02:06)
Immunogen	HIV-1 infection
Country	Japan
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Other
Keywords	optimal epitope, chronic infection

Notes

CTL controlling HIV-1 and variants were identified from 401 subtype B chronically-infected, treatment-naive Japanese patients. 7 novel epitopes were identified (paper reports 9, correction made via author communication). 9/13 CTL-specific epitopes were conserved among the above subjects and 3/13 were cross-recognized by CTL. 5/13 epitopes were B*5201, 3/13 were B*6701-restricted, both HLA were found to play a predominant role in control of HIV-1. This is the first study to identify HIV-1-specific T cells clinically controlling HIV-1 in a population in whom protective HLA-B*57 and HLA-B*27 are very rare.
Breadth of response of all 13 epitope-specific CTL had synergistic effects on control, directly correlating to CD4 cell count and inversely to plasma viral load (pVL).
HLA-A*0206-restricted GagAA9, ATLEEMMTA, had 30/393 responding subjects and did significantly correlate with pVL or CD4 count, suggesting A*0206 could be a protective allele. AA9 is a conserved epitope.

References

Murakoshi2015 Hayato Murakoshi, Tomohiro Akahoshi, Madoka Koyanagi, Takayuki Chikata, Takuya Naruto, Rie Maruyama, Yoshiko Tamura, Naoki Ishizuka, Hiroyuki Gatanaga, Shinichi Oka, and Masafumi Takiguchi. Clinical Control of HIV-1 by Cytotoxic T Cells Specific for Multiple Conserved Epitopes. J. Virol., 89(10):5330-5339, May 2015. PubMed ID: 25741000. Show all entries for this paper.

Displaying record number 61546

Download this epitope record as JSON.

HXB2 Location	Gag(341-349) p24(209-217) DNA(1810..1836)	Gag Epitope Map
Author Location	p24(207-219)
Epitope	`ATLEEMMTA`	Epitope Alignment
Epitope Name	Gag AA9
Subtype	B, CRF01_AE
Species (MHC/HLA)	human(A*02:06)
Immunogen	HIV-1 infection
Patient MHC/HLA	KI-648: A*02:06
Country	Japan
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining
Keywords	optimal epitope, chronic infection

Notes

Polymorphic epitope regions can be targets for cross-clade CTL response. In addition to 6 conserved AE epitopes, 9 epitopes polymorphic between clades AE and B were identified in chronically infected Japanese subjects. This is the first comprehensive study to identify cross-clade CTL by using overlapping HIV-1 peptides.
There were no significant differences in total magnitude of CTL response between 26 clade A/E-infected and 401 clade B-infected subjects when tested with 11-mers from HIV-B Nef, Gag and Pol. 6 epitopes were novel viz. Gag LL11, Pol SV9, Pol GI9, Gag RV8, Gag AP8 and Gag EG11.
Epitope Gag p24 AA9, ATLEEMMTA, is conserved between clades B and A/E and was found in 1468/1644 Clade B and 285/315 Clade A/E Los Alamos database HIV-1 sequences. It was found in 25/26 A/E-infected subjects of the KI cohort.

References

Watanabe2013 Koji Watanabe, Hayato Murakoshi, Yoshiko Tamura, Madoka Koyanagi, Takayuki Chikata, Hiroyuki Gatanaga, Shinichi Oka, and Masafumi Takiguchi. Identification of Cross-Clade CTL Epitopes in HIV-1 Clade A/E-Infected Individuals by Using the Clade B Overlapping Peptides. Microbes Infect., 15(13):874-886, Nov 2013. PubMed ID: 23968885. Show all entries for this paper.

Displaying record number 61789

Download this epitope record as JSON.

HXB2 Location	Gag(341-349) p24(209-217) DNA(1810..1836)	Gag Epitope Map
Author Location
Epitope	`ATLEEMMTA`	Epitope Alignment
Epitope Name	AA9
Subtype	B
Species (MHC/HLA)	human(A*02:06)
Immunogen	HIV-1 infection, vaccine
Country	Japan
Experimental methods	CD8 T-cell Elispot - IFNγ, CTL suppression of replication, Intracellular cytokine staining
Keywords	vaccine-induced immune responses, variant cross-reactivity

Notes

Specific T cells - from 120 ART-naive, infected Japanese subjects previously exposed to the tHIVconsvX vaccine - that have the ability to suppress HIV-1 replication were identified as recognizing 17 optimal Gag epitopes. 9/17 eptiopes were associated with lower pVL and higher CD4 count, of which 5 remain associated with positive clinical outcome in 221 HIV-1 infected subjects and cross-recognized major HIV-1 variants. 2/5 epitopes were novel. Candidate tHIVconsvX vaccine is composed of 6 conserved Gag and Pol regions.
A*0206-restricted epitope ATLEEMMTA was found in 15-mer peptide pairs C102/103 and C104. 5 HLA-Cw*08-carrying responders to this epitope were detected by EliSpot out of 53 subjects.

References

Murakoshi2018 Hayato Murakoshi, Chengcheng Zou, Nozomi Kuse, Tomohiro Akahoshi, Takayuki Chikata, Hiroyuki Gatanaga, Shinichi Oka, Tomáš Hanke, and Masafumi Takiguchi. CD8+ T Cells Specific for Conserved, Cross-Reactive Gag Epitopes with Strong Ability to Suppress HIV-1 Replication. Retrovirology, 15(1):46, 3 Jul 2018. PubMed ID: 29970102. Show all entries for this paper.

Displaying record number 54207

Download this epitope record as JSON.

HXB2 Location	Gag(341-349) p24(209-217) DNA(1810..1836)	Gag Epitope Map
Author Location	Gag
Epitope	`ATLEEMMTA`	Epitope Alignment
Subtype	CRF01_AE
Species (MHC/HLA)	human(A*02:06)
Immunogen	HIV-1 infection
Country	Thailand
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay
Keywords	optimal epitope

Notes

T cell responses in CRF01_AE infected individuals from Thailand were studied. Fine mapping of the peptides containing potentially novel epitopes revealed novel restriction of a previously identified epitope in this population.
A novel restriction allele for this epitope (ATLEEMMTA) was found, HLA-A*0206.

References

Kantakamalakul2006 Wannee Kantakamalakul, Mark De Souza, Sasitorn Bejrachandra, Silawun Ampol, Josephine Cox, and Ruengpung Sutthent. Identification of a Novel HIV Type 1 CRF01\_AE Cytotoxic T Lymphocyte (CTL) Epitope Restricted by an HLA-Cw0602 Allele and a Novel HLA-A0206/Peptide Restriction. AIDS Res. Hum. Retroviruses, 22(12):1271-1282, Dec 2006. PubMed ID: 17209771. Show all entries for this paper.

Displaying record number 61883

Download this epitope record as JSON.

HXB2 Location	Gag(341-349) p24(209-217) DNA(1810..1836)	Gag Epitope Map
Author Location
Epitope	`ATLEEMMTA`	Epitope Alignment
		Show epitope variants
Epitope Name	Gag AA9
Subtype	B
Species (MHC/HLA)	human(A*02:06)
Immunogen	HIV-1 infection, vaccine
Patient MHC/HLA	KI-611: A*02:06
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Other
Keywords	vaccine-induced immune responses, viral replication

Notes

CTL specific for 10 epitopes that are associated with good clinical outcomes (Murakoshi2018, Zou2019) were shown to have strong ability to suppress HIV-1 replication. These CTL could recognize HIV-1-infected cells and most circulating HIV-1 in Japan as the 5 HLA-alleles restricting these 10 epitopes are represented in >50% of the Japanese population surveyed.
A*0206-restricted protective epitope, ATLEEMMTA, Gag AA9 was found in 89.5% chronically infected Japanese individuals and 84.9% of them who were A*0206+. Variants of this WT epitope were found too, AsLEEMMTA, AA9-2S, ATLEEMMaA, AA9-8A, ATLEEMMsA, AA9-8S, and pTLEEMMTA, AA9-1P. All variants were cross-recognized by AA9-specific CTL.

References

Murakoshi2019 Hayato Murakoshi, Nozomi Kuse, Tomohiro Akahoshi, Yu Zhang, Takayuki Chikata, Mohamed Ali Borghan, Hiroyuki Gatanaga, Shinichi Oka, Keiko Sakai, and Masafumi Takiguchi. Broad Recognition of Circulating HIV-1 by HIV-1-Specific Cytotoxic T-Lymphocytes with Strong Ability to Suppress HIV-1 Replication. J. Virol., 93(1), 1 Jan 2019. PubMed ID: 30333175. Show all entries for this paper.

Displaying record number 52681

Download this epitope record as JSON.

HXB2 Location	Gag(341-349) p24(209-217) DNA(1810..1836)	Gag Epitope Map
Author Location	Gag(341-)
Epitope	`ATLEEMMTA`	Epitope Alignment
Epitope Name	Gag341
Species (MHC/HLA)	human, transgenic mouse(A2)
Immunogen	HIV-1 infection, vaccine
Experimental methods	CD8 T-cell Elispot - IFNγ, Chromium-release assay, Flow cytometric T-cell cytokine assay
Keywords	binding affinity, subtype comparisons, computational epitope prediction

Vaccine Details

Vaccine type	peptide
Vaccine component	p24 Gag
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 did not induce CTL and CD8+ T-cell IFN gamma responses in mice, although responses were detected in 2/17 HIV+ HLA-A2 subjects.

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 55369

Download this epitope record as JSON.

HXB2 Location	Gag(341-349) p24(209-217) DNA(1810..1836)	Gag Epitope Map
Author Location
Epitope	`ATLEEMMTA`	Epitope Alignment
Epitope Name	Gag 341
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

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 341 ATLEEMMTA epitope was highly conserved and found in all 11 patients but only 2 had CTL immune responses to it.

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 55889

Download this epitope record as JSON.

HXB2 Location	Gag(341-349) p24(209-217) DNA(1810..1836)	Gag Epitope Map
Author Location	Gag
Epitope	`ATLEEMMTA`	Epitope Alignment
Subtype	B, D
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Country	Sweden
Experimental methods	CD8 T-cell Elispot - IFNγ, Other
Keywords	subtype comparisons

Notes

By studying Gag p24 in different subtypes of subjects, previously discovered and new epitopes were identified. New T cell epitopes, both CD8 and CD4, related to the patients' HLA are described.
T cells cross-reacted to peptides from different patient subtypes, and this cross-reactivity was distributed along the entire p24 protein.
HLA-A2-restricted epitope ATLEEMMTA is from a subtype B peptide library, and is reactive as part of peptide ATLEEMMTACQGVGG in a subtype D-carrying subject.

References

Gudmundsdotter2008 L. Gudmundsdotter, D. Bernasconi, B. Hejdeman, E. Sandstrom, A. Alaeus, K. Lidman, B. Ensoli, B. Wahren, and S. Buttò. Cross-Clade Immune Responses to Gag p24 in Patients Infected with Different HIV-1 Subtypes and Correlation with HLA Class I and II Alleles. Vaccine, 26(40):5182-5187, 19 Sep 2008. PubMed ID: 18479789. Show all entries for this paper.

Displaying record number 56058

Download this epitope record as JSON.

HXB2 Location	Gag(341-349) p24(209-217) DNA(1810..1836)	Gag Epitope Map
Author Location	Gag(341-)
Epitope	`ATLEEMMTA`	Epitope Alignment
Epitope Name	Gag341
Species (MHC/HLA)	human(A2)
Immunogen	HIV-1 infection
Country	Denmark
Experimental methods	Flow cytometric T-cell cytokine assay
Keywords	rate of progression, 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 ATLEEMMTA, though it did elicit response in a cohort of 11 other HIV-1+ HLA-A2+ patients.

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 58947

Download this epitope record as JSON.

HXB2 Location	Gag(341-349) p24(209-217) DNA(1810..1836)	Gag Epitope Map
Author Location	Gag
Epitope	`ATLEEMMTA`	Epitope Alignment
Subtype	A
Species (MHC/HLA)	human
Immunogen	HIV-1 infection
Country	Kenya, Pakistan
Experimental methods	Other
Keywords	epitope processing

Notes

To compare epitopes generated in diverse genetic populations due to the mutations that affect respective antigen processing, 29 Kenyan and 56 Pakistani subjects infected with HIV-1 subtype A were studied. HIV-1 Gag was sequenced for mutations affecting proteasomal degradation, TAP or HLA binding and CTL epitope generation. Epitope patterns were found to be altered due to population-specific mutations in epitope-generating pathways.
Several predicted epitopes of differential frequency were shown in this study (see Table 1). Only epitopes immunologically verified previously are annotated here.
Epitope ATLEEMMTA was generated from HIV-1 subtype A for HLA-presentation in both Kenyan and Pakistani populations.

References

Abidi2013 Syed H. Abidi, Aniqa Shahid, Laila S. Lakhani, Muhammad R. Khanani, Peter Ojwang, Nancy Okinda, Reena Shah, Farhat Abbas, Sarah Rowland-Jones, and Syed Ali. Population-Specific Evolution of HIV Gag Epitopes in Genetically Diverged Patients. Infect. Genet. Evol., 16:78-86, Jun 2013. PubMed ID: 23403357. Show all entries for this paper.