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Displaying record number 58818

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HXB2 Location	gp160(59-69) gp120(59-69) DNA(6399..6431)	gp160 Epitope Map
Author Location	Env(81-89)
Epitope	KAYEKEVHNVW	Epitope Alignment
Subtype	C
Species (MHC/HLA)	human(B*57:03, B*58:01)
Immunogen	HIV-1 infection
Country	Botswana, South Africa, Zimbabwe
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding, Tetramer binding
Keywords	optimal epitope

Notes

• 1,010-HIV C clade-chronically infected subjects were tested in order to distinguish levels of immune control by related but different HLA-B*57/58. B*57 micropolymorphisms (B*5703 and B*5702) as well as B*5801 have differing CTL specificity and also present different p24 Gag epitopes. This results in different immune selection pressures on the HIV-C virus.
• Though all three studied HLA alleles, B*5801, B*5702 and B*5703 are significantly associated with lower viral-load (VL) set points, HLA-B*5703, followed closely by B*5702 is the most potent controller with lowest VL and HLA-B*5702, followed by B*5703 and then B*5801 are associated with highest CD4 counts.
• By using 410 overlapping 18-mers that span the HIV-C proteome in EliSpot assays, 17 epitopes were identified that are presented by one of HLAs-B*5801/5702/5703, 13 of them novel.
• Epitope KAYEKEVHNVW was known to be restricted by HLA-B*5703 and -B*5801, with 40% of B*5801-responders recognizing it. 10% B*5702- and >15% B*5703-responders also recognized it. It was confirmed to be optimal by peptide truncation using B*5801-restricted CTL from chronically infected subject R076.
• The binding affinity of KAYEKEVHNVW is greatest to B*5702 and its binding to B*5801 has greatest stability .
• >70% B*5702- and B*5801-positive, ˜60% B*5703 and non-B*57 carried mutations in KAYEKEVHNVW.

References

Kloverpris2012 Henrik N. Kloverpris, Anette Stryhn, Mikkel Harndahl, Mary van der Stok, Rebecca P. Payne, Philippa C. Matthews, Fabian Chen, Lynn Riddell, Bruce D. Walker, Thumbi Ndung'u, Søren Buus, and Philip Goulder. HLA-B*57 Micropolymorphism Shapes HLA Allele-Specific Epitope Immunogenicity, Selection Pressure, and HIV Immune Control. J. Virol., 86(2):919-929, Jan 2012. PubMed ID: 22090105. Show all entries for this paper.