Details

Autor(en) / Beteiligte

• Sun, Xiaoming
• Shi, Yi
• Akahoshi, Tomohiro
• Fujiwara, Mamoru
• Gatanaga, Hiroyuki
• Schönbach, Christian
• Kuse, Nozomi
• Appay, Victor
• Gao, George F.
• Oka, Shinichi
• Takiguchi, Masafumi

Titel

Effects of a Single Escape Mutation on T Cell and HIV-1 Co-adaptation

Ist Teil von

• Cell reports (Cambridge), 2016-06, Vol.15 (10), p.2279-2291

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •A single mutation in two superimposed epitopes induces distinct immune responses•The mutation induces a new T cell repertoire for one epitope but not the other•The immune variant affects T cell recognition by reducing pMHC-complex stability•HLA-binding stability and antigen structural features determine immune outcomes Rational design of T cell vaccines requires understanding of T cell and HIV-1 co-evolution. Sun et al. find that a single immune escape mutation has differential impacts on two HIV epitope-specific responses. The mutation alters the ability of the virus to trigger immune responses.