Effects of a Single Escape Mutation on T Cell and HIV-1 Co-adaptation
Loading...
Date
2016-06-07
Authors
Sun, Xiaoming
Shi, Yi
Akahoshi, Tomohiro
Fujiwara, Mamoru
Gatanaga, Hiroyuki
Schönbach, Christian
Kuse, Nozomi
Appay, Victor
Gao, George F.
Journal Title
Journal ISSN
Volume Title
Publisher
Cell Reports
Abstract
Summary The mechanistic basis for the progressive accumulation of Y135F Nef mutant viruses in the HIV-1-infected population remains poorly understood. Y135F viruses carry the 2F mutation within RW8 and RF10, which are two HLA-A∗24:02-restricted superimposed Nef epitopes recognized by distinct and adaptable CD8+ T cell responses. We combined comprehensive analysis of the T cell receptor repertoire and cross-reactive potential of wild-type or 2F RW8- and RF10-specific CD8+ T cells with peptide-MHC complex stability and crystal structure studies. We find that, by affecting direct and water-mediated hydrogen bond networks within the peptide-MHC complex, the 2F mutation reduces both TCR and HLA binding. This suggests an advantage underlying the evolution of the 2F variant with decreased CD8+ T cell efficacy. Our study provides a refined understanding of HIV-1 and CD8+ T cell co-adaptation at the population level.
Description
Keywords
Citation
Xiaoming Sun, Yi Shi, Tomohiro Akahoshi, Mamoru Fujiwara, Hiroyuki Gatanaga, Christian Schönbach, Nozomi Kuse, Victor Appay, George F. Gao, Shinichi Oka, Masafumi Takiguchi, Effects of a Single Escape Mutation on T Cell and HIV-1 Co-adaptation, In Cell Reports, Volume 15, Issue 10, 2016, Pages 2279-2291