Search CTL/CD8+ T-Cell Epitope Database

Found 5 matching records:

Displaying record number 58600

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HXB2 Location	Gag(253-262) p24(121-130) DNA(1546..1575)	Gag Epitope Map
Author Location	Gag(253-262)
Epitope	NPPIPVGDIY	Epitope Alignment
		Show epitope variants
Epitope Name	NY10, NY10-260D
Subtype	C
Species (MHC/HLA)	human(B*35:01)
Immunogen	HIV-1 infection
Country	Barbados, Botswana, Haiti, Japan, Mexico, South Africa, United Kingdom, United States
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding, Intracellular cytokine staining, Tetramer binding
Keywords	subtype comparisons, optimal epitope

Notes

• While host HLA Class I genotype is the major genetic determinant of HIV-1 progression to AIDS, the same HLA allele could have varying outcomes for different infecting HIV clades. Overall, p24 Gag-specific epitopes were targeted significantly more frequently by C-clade-infected B*3501-positive subjects (55%) than B-clade-carrying B*3501-subjects (31%), while Env-specific epitopes were targeted more frequently by B-clade-infected subjects.
• In general HLA-B*3501-restricted epitopes, were not targeted differentially for different clades. In contrast, CTL targeting against B*3501-restricted clade C Gag epitope, NPPIPVGDIY (NY10) but not clade B NY10, was associated with a lower viral set point and higher absolute CD4 count, i.e. better disease control. The above major result for epitope NY10 was confirmed for the B clade variant in Caucasian, Japanese and Mexican cohorts; C clade results were confirmed in South African (Durban) and Botswanan (Gaborne) cohorts.
• In addition 5 new C-clade epitopes were identified.
• For this epitope, NY10, the 10-mer, NPPIPVGDIY was shown to be optimal. This form, position 8 260D, is the Clade C form and NY10-260E is the Clade C escape form as well as the major Clade B form. NY10-260D binds B*3501 with >10x binding affinity and >3x binding stability than the 260E form does. CTL response to NY10 260D was detected in >30% of C-clade infected subjects.

References

Matthews2012 Philippa C. Matthews, Madoka Koyanagi, Henrik N. Kløverpris, Mikkel Harndahl, Anette Stryhn, Tomohiro Akahoshi, Hiroyuki Gatanaga, Shinichi Oka, Claudia Juarez Molina, Humberto Valenzuela Ponce, Santiago Avila Rios, David Cole, Jonathan Carlson, Rebecca P. Payne, Anthony Ogwu, Alfred Bere, Thumbi Ndung'u, Kamini Gounder, Fabian Chen, Lynn Riddell, Graz Luzzi, Roger Shapiro, Christian Brander, Bruce Walker, Andrew K. Sewell, Gustavo Reyes Teran, David Heckerman, Eric Hunter, Søren Buus, Masafumi Takiguchi, and Philip J. R. Goulder. Differential Clade-Specific HLA-B*3501 Association with HIV-1 Disease Outcome Is Linked to Immunogenicity of a Single Gag Epitope. J. Virol., 86(23):12643-12654, Dec 2012. PubMed ID: 22973023. Show all entries for this paper.

Displaying record number 58627

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HXB2 Location	Gag(253-262) p24(121-130) DNA(1546..1575)	Gag Epitope Map
Author Location
Epitope	NPPIPVGDIY	Epitope Alignment
Species (MHC/HLA)	human(B*35:01)
Immunogen
Experimental methods
Keywords	optimal epitope, A-list

Notes

• C. Brander noted this as an optimal B*3501 epitope based on data from Matthews2012.

References

Llano2019 Anuska Llano, Samandhy Cedeño, Sandra Silva Arrieta, and Christian Brander. The 2019 Optimal HIV CTL Epitopes Update: Growing Diversity in Epitope Length and HLA restriction. 2019. Show all entries for this paper.

Displaying record number 61211

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HXB2 Location	Gag(253-262) p24(121-130) DNA(1546..1575)	Gag Epitope Map
Author Location	Gag(254-262)
Epitope	NPPIPVGDIY	Epitope Alignment
		Show epitope variants
Epitope Name	NY10
Subtype	B
Species (MHC/HLA)	human(B*35:01)
Immunogen	HIV-1 infection
Experimental methods	Other
Keywords	review, escape, HLA associated polymorphism

Notes

• This review follows protective HLA-I molecules and their conserved p24 Gag epitopes that escape with a fitness cost to viral replicative capacity (VRC). Compensatory viral mutations can correct for VRC loss to different extents. This results in protective HLA losing impact as well as a modest decline in virulence of HIV with reduced VRC.
• Epitope NY10, NPPIPVGDIY, is restricted by B*3501. An escape is found at D260E.

References

Kloverpris2015a Henrik N. Kløverpris, Alasdair Leslie, and Philip Goulder. Role of HLA Adaptation in HIV Evolution. Front. Immunol., 6:665, 18 Jan 2016. PubMed ID: 26834742. Show all entries for this paper.

Displaying record number 59119

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HXB2 Location	Gag(253-262) p24(121-130) DNA(1546..1575)	Gag Epitope Map
Author Location	Gag(253-262)
Epitope	NPPIPVGDIY	Epitope Alignment
		Show epitope variants
Epitope Name	NY10
Subtype	CRF01_AE
Species (MHC/HLA)	human(B*35:01, B*35:05)
Immunogen	HIV-1 infection
Patient MHC/HLA	P206: A*02:03, A*11:02, B*18:02, B*35:01, C*04:01, C*07:04; P381: A*11:01, A*33:03, B*15:02, B*35:01, C*04:01, C*08:01; P453: A*24:02, B*15:25, B*35:01, C*07:02, C*12:03; P1349: A*02:03, A*11:01, B*35:01, B*38:02, C*03:03, C*07:02; P2097: A*24:02, A*31:01, B*35:01, B*46:01, C*01:02, C*04:01; P115: A*02:06, A*11:01, B*35:05, B*46:01, C*01:02, C*04:01; P1013: A*02:03, A*11:01, B*35:05, B*52:01, C*04:01, C*07:01; P1497: A*02:01, A*11:01, B*13:01, B*35:05, C*04:01, C*04:06; P1651: A*02:06, A*11:01, B*35:05, B*40:06, C*04:01, C*08:01
Country	Thailand
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	structure, HLA associated polymorphism

Notes

• HLA-B*3505 was identified as a protective HLA allele in the Lampang cohort of HIV-1 CRF01_AE-infected Thais. While HLA-B*5801 is not protective in this cohort, HLA-B*57 is but its frequency is low, at 1.4%. B*3505 is a structural variant of B*3501, both belonging to the B*35-PY group of HLA.
• Epitope NY10, NPPIPVGDIY, was used to study structural determinants in the binding grooves of HLA-B*35. No variants in NY10 were seen when restricted by HLA-B*3505.

References

Mori2014 Masahiko Mori, Nuanjun Wichukchinda, Reiko Miyahara, Archawin Rojanawiwat, Panita Pathipvanich, Tomoyuki Maekawa, Toshiyuki Miura, Philip Goulder, Michio Yasunami, Koya Ariyoshi, and Pathom Sawanpanyalert. HLA-B*35:05 Is a Protective Allele with a Unique Structure among HIV-1 CRF01\_AE-Infected Thais, in Whom the B*57 Frequency Is Low. AIDS, 28(7):959-967, 24 Apr 2014. PubMed ID: 24566094. Show all entries for this paper.

Displaying record number 62805

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HXB2 Location	Gag(253-262) p24(121-130) DNA(1546..1575)	Gag Epitope Map
Author Location	p24(253-262)
Epitope	NPPIPVGDIY	Epitope Alignment
Subtype	B
Species (MHC/HLA)	human
Immunogen	engineered
Experimental methods	Other, Relative replication capacity assay
Keywords	assay or method development, protective allele

Notes

• NL4-3 Gag polyprotein random mutagenesis, high-throughput fitness profiling and in silico prediction of MHC-peptide binding affinity revealed that mutations in CTL epitopes presented by protective MHC-I alleles, vs. non-protective alleles, showed greater loss of experimental replicative capacity and lower levels of predicted reduction in MHC-I binding affinity. Together, these two variables could predict protectiveness of MHC-I alleles in a linear regression model. Analyses of intraperson viral evolution in 4 LTNP vs. 4 paired progressor subjects further supported paper conclusions.
• After mutagenesis and passaging through human T cells, 65 single nucleotide mutations were observed in epitope NPPIPVGDIY (known to bind to B3501) with a log transformation of mean fitness score, relative to NL4-3, of -0.5597.

References

Du2017 Yushen Du, Tian-Hao Zhang, Lei Dai, Xiaojuan Zheng, Aleksandr M. Gorin, John Oishi, Ting-Ting Wu, Janice M. Yoshizawa, Xinmin Li, Otto O. Yang, Otoniel Martinez-Maza, Roger Detels, and Ren Sun. Effects of Mutations on Replicative Fitness and Major Histocompatibility Complex Class I Binding Affinity Are Among the Determinants Underlying Cytotoxic-T-Lymphocyte Escape of HIV-1 Gag Epitopes. mBio, 8(6), 28 Nov 2017. PubMed ID: 29184023. Show all entries for this paper.