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Displaying record number 59203

HXB2 Location	Nef(126-135) DNA(9172..9201)	Nef Epitope Map
Author Location	Nef(126-135)
Epitope	NYTPGPGIRY	Epitope Alignment
		Show epitope variants
Epitope Name	Nef126-10
Subtype	B
Species (MHC/HLA)	human(A*2402)
Immunogen	HIV-1 infection
Country	Canada, Japan
Experimental methods	CD8 T-cell Elispot - IFNγ, HLA binding, Other
Keywords	escape, structure, novel epitope

Notes

• CTL epitope switching was studied in 46 HLA-A*2402+ Japanese patients from the IMSUT and HOMER cohorts. 76% harbored the Y135F mutation in Nef, a predominant escape in A*2402+ Japanese populations and this de novo creates a novel overlapping CTL epitope, Nef 134-10. The Nef 134-10 epitope, containing 135Y escapes to 135F, forming the Nef126-10 epitope instead.
• Nef 126-10, NYTPGPGIRY, contains the HXB-2 135Y sequence, seen in 8/46 subjects and is recognized endogenously, with an 50% subject-response rate. None of the 8 subjects exhibited a Nef126-10 response. The Y135F mutation in Nef134-10(2F) was almost as effective at HLA binding as the wild type (wt); and Nef134-10-specific CTL clones produced IFN-γ almost as well to wt or 2F peptides. In the context of the Nef126-10 epitope, however, the same Y135F mutation dramatically increased binding to HLA; and Nef126-10-specific CTL clones produced IFN-&gamma only to high wt peptide concentrations. Mutant peptides of 126-10, however (i.e. NYTPGPGIRf and NYTPGPGtRf), induced strong response at low concentration.
• One patient subsequently selected Y135F, followed by 133T over a year. Most CTL responses were to Nef134-10(wt) followed by responses to Nef134-10(2F) initially, while there were no Nef126-10 responses at that time. After variation to 133T/135F, robust responses were detected to Nef126-10(8I10F) and Nef126-10(8T10F), but responses to Nef126-10(wt) were only at high concentrations. By this time responses to Nef134-10 were detectable though decreased.
• A positive correlation was seen between Nef135F and Nef133T as well as between Nef135Y and Nef133I. Selection of 135F precedes 133T by a short duration.

References

Han2014 Chungyong Han, Ai Kawana-Tachikawa, Akihisa Shimizu, Dayong Zhu, Hitomi Nakamura, Eisuke Adachi, Tadashi Kikuchi, Michiko Koga, Tomohiko Koibuchi, George F. Gao, Yusuke Sato, Atsushi Yamagata, Eric Martin, Shuya Fukai, Zabrina L. Brumme, and Aikichi Iwamoto. Switching and Emergence of CTL Epitopes in HIV-1 Infection. Retrovirology, 11:38, 2014. PubMed ID: 24886641. Show all entries for this paper.

Displaying record number 61736

HXB2 Location	Nef(126-135) DNA(9172..9201)	Nef Epitope Map
Author Location	Nef(126-135)
Epitope	NYTPGPGIRY	Epitope Alignment
Epitope Name	NY10
Species (MHC/HLA)	human(A*2402)
Immunogen
Experimental methods
Keywords	optimal epitope

Notes

• C. Brander notes this as an A*2402-restricted Nef epitope (Han2014, unpublished data).

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.