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Displaying record number 61680

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HXB2 Location	Nef(116-124) DNA(9142..9168)	Nef Epitope Map
Author Location	Nef(116-124)
Epitope	HTQGFFPDW	Epitope Alignment
		Show epitope variants
Epitope Name	Nef-HW9
Subtype	C
Species (MHC/HLA)	human(B*35:01, B*53:01)
Immunogen	HIV-1 infection
Country	Botswana, South Africa, United Kingdom, Zimbabwe
Experimental methods	CD8 T-cell Elispot - IFNγ
Keywords	HLA associated polymorphism

Notes

• Since CTL targeting frequency and risk of immune escape are dependent on the genetic context in which the epitope is presented, systematic computational analyses of differential patterns of immune escape across all optimally defined epitopes in Gag, Pol and Nef in 2,126 HIV-1 clade C-infected adults were performed. 301 polymorphisms were identified in 90 epitopes associated with HLA alleles belonging to shared supertypes, while 37/38 eptiopes restricted by more than one HLA allele represented 278 instances of differential polymorphic escape. 66-97% of these polymorphisms tested were the result of unique HLA-specific polymorphisms rather than differential epitope targeting rates. Total number of polymorphisms also strongly correlated with average VL (viral load).
• Differential escape among protective B58-supertype alleles were studied. A polymorphism of Nef optimal epitope, HW9, HTQGFFPDW, was seen. Wt HTQGFFPDW as well as P1 escape, nTQGFFPDW were more significantly associated with B*5703 than with B*5801.

References

Carlson2012 Jonathan M. Carlson, Jennifer Listgarten, Nico Pfeifer, Vincent Tan, Carl Kadie, Bruce D. Walker, Thumbi Ndung'u, Roger Shapiro, John Frater, Zabrina L. Brumme, Philip J. R. Goulder, and David Heckerman. Widespread Impact of HLA Restriction on Immune Control and Escape Pathways of HIV-1. J. Virol., 86(9):5230-5243, May 2012. PubMed ID: 22379086. Show all entries for this paper.

Displaying record number 58820

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HXB2 Location	Nef(116-124) DNA(9142..9168)	Nef Epitope Map
Author Location	Nef(81-89)
Epitope	HTQGFFPDW	Epitope Alignment
Epitope Name	HW9
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, Intracellular cytokine staining, Tetramer binding
Keywords	optimal epitope, HLA associated polymorphism, novel 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.
• Novel epitope HW9 Nef, HTQGFFPDW, was confirmed to be optimal by peptide truncation and restricted by HLA-B*5703, B*5801 using CTL from chronically infected subjects R046, N087.
• The binding affinity and stability of HW9 is greatest to B*5703; >30% B*5801-responders recognized HW9, >20% B*5703-responders recognized it, and ∼10% B*5702-responders recognized HW9 Nef.
• Near 100% B*5703- and B*5801-positive subjects carried mutations in HW9. ˜70% of B*5702 and and even ˜60% nonB*57-positive subjects sustained HW9 variations.

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.