5HGA

HLA*A2402 complex with HIV nef138 Y2F-8mer mutant epitope

Summary for 5HGA

• Entry DOI: 10.2210/pdb5hga/pdb
• Related: 5HGB 5HGD 5HGH
• Descriptor: HLA class I histocompatibility antigen, A-24 alpha chain, Beta-2-microglobulin, 8-mer from Protein Nef, ... (4 entities in total)
• Functional Keywords: hla, antigen presentation, hiv, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 89173.27

Authors

Shi, Y.,Qi, J.,Gao, G.F. (deposition date: 2016-01-08, release date: 2016-06-08, Last modification date: 2024-10-23)

Primary citation

Sun, X.,Shi, Y.,Akahoshi, T.,Fujiwara, M.,Gatanaga, H.,Schonbach, C.,Kuse, N.,Appay, V.,Gao, G.F.,Oka, S.,Takiguchi, M.
Effects of a Single Escape Mutation on T Cell and HIV-1 Co-adaptation.
Cell Rep, 15:2279-2291, 2016

PubMed Abstract: The mechanistic basis for the progressive accumulation of Y(135)F Nef mutant viruses in the HIV-1-infected population remains poorly understood. Y(135)F 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.

PubMed: 27239036
DOI: 10.1016/j.celrep.2016.05.017

Experimental method

X-RAY DIFFRACTION (2.199 Å)