Search CTL/CD8+ T-Cell Epitope Database

Found 5 matching records:

Displaying record number 61148

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HXB2 Location	Gag(316-323) p24(184-191) DNA(1735..1758)	Gag Epitope Map
Author Location
Epitope	WMTETLLV	Epitope Alignment
		Show epitope variants
Subtype	B
Species (MHC/HLA)	human, mouse(B*52:01)
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

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 WMTETLLV was present in mosaic 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 61496

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HXB2 Location	Gag(316-323) p24(184-191) DNA(1735..1758)	Gag Epitope Map
Author Location	Gag
Epitope	WMTETLLV	Epitope Alignment
Epitope Name	WV8
Subtype	B
Species (MHC/HLA)	human(B*52:01)
Immunogen	HIV-1 infection
Country	Japan
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	chronic infection

Notes

• HLA-B*5201-C*1202 haplotype which has strong linkage disequilibrium and is found in approximately 20% Japanese,, is protective during HIV-1 infection by suppression of HIV-1 replication via CTL and NK cells. Cw*1202 is known to work with KIR2DL2 in NK-cell mediated control.
• HLA-B*5201-restricted HIV-1 WV8(WMTETLLV) was correlated inversely with pVL (plasma viral load) and positively with CD4+ T cell count in HLA-B*5201-Cw*1202 responders versus non-responders. EliSpot responses were strong.

References

Chikata2017 Takayuki Chikata, Hayato Murakoshi, Madoka Koyanagi, Kazutaka Honda, Hiroyuki Gatanaga, Shinichi Oka, and Masafumi Takiguchi. Control of HIV-1 by an HLA-B*52:01-C*12:02 Protective Haplotype. J. Infect. Dis., 216(11):1415-1424, 12 Dec 2017. PubMed ID: 28968792. Show all entries for this paper.

Displaying record number 61508

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HXB2 Location	Gag(316-323) p24(184-191) DNA(1735..1758)	Gag Epitope Map
Author Location	Gag(316-323)
Epitope	WMTETLLV	Epitope Alignment
Epitope Name	GagWV8
Subtype	B
Species (MHC/HLA)	human(B*52:01)
Immunogen	HIV-1 infection
Country	Japan
Experimental methods	CD8 T-cell Elispot - IFNγ, Intracellular cytokine staining, Other
Keywords	optimal epitope, novel 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).
• Novel epitope, HLA-B*5201-restricted GagWV8, WMTETLLV, had 43/393 responding subjects and did significantly correlate with pVL or CD4 count, confirming B*5201 as a protective allele. WV8 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 61785

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HXB2 Location	Gag(316-323) p24(184-191) DNA(1735..1758)	Gag Epitope Map
Author Location
Epitope	WMTETLLV	Epitope Alignment
Epitope Name	WV8
Subtype	B
Species (MHC/HLA)	human(B*52:01)
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.
• B*5201-restricted epitope YVDRFYKTL was found in 15-mer peptide pair C088/089. 6 HLA-B*5201-carrying responders to this epitope were detected by EliSpot out of 50 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 61879

Download this epitope record as JSON.

HXB2 Location	Gag(316-323) p24(184-191) DNA(1735..1758)	Gag Epitope Map
Author Location
Epitope	WMTETLLV	Epitope Alignment
		Show epitope variants
Epitope Name	Gag WV8
Subtype	B
Species (MHC/HLA)	human(B*52:01)
Immunogen	HIV-1 infection, vaccine
Patient MHC/HLA	KI-774: B*52:01; KI-687: B*52:01
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.
• B*5201-restricted protective epitope, WMTETLLV, Gag WV8 was found in 97% chronically infected Japanese individuals and 96.8% of them who were B*5201+. A variant of this WT epitope was found too, WMTdTLLV, WV8-4D. WV8-4D was not recognized by WV8-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.