Molecular basis for selection and inhibition of HIV-1 escape virus by T cells and KIR2DL2+NK cells

作者：Takayuki Chikata, Kimiko Kuroki, Nozomi Kuse, Anna E. Kliszczak, Wayne Paes, Nanami Tomioka, Robert Parker, Aure Aflalo, Tomohiro Akahoshi, Yu Zhang, Ryoya Yamashita, Ryuma Sakata, Hiroki Kusaka, Yosuke Watanabe, Annalisa Nicastri, Haruki Matsubara, Toyoyuki Ose, Shunsuke Kita, Shinichi Oka, Hiroyuki Gatanaga, Zhansong Lin, Nicola Ternette, Persephone Borrow, Katsumi Maenaka, Masafumi Takiguchi · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-64768-2 · 被引用次数：1 · 研究领域：Immune Cell Function and Interaction、HIV Research and Treatment、T-cell and B-cell Immunology

NK cells and CD8+ T cells both contribute to HIV-1 control. These cells not only suppress HIV-1 replication, but also select HIV-1 escape mutant viruses. Most viruses bearing T cell escape mutations are expected to remain susceptible to NK cell suppression, but their inhibition by NK cells is unclear. We investigated the role of HIV-1-specific CD8+ T cells and NK cells recognizing superimposed Pol peptides in selection and control of HIV-1 mutant virus. KIR2DL2+NK cells have an enhanced ability to recognize HIV-1-infected cells after selection of Pol mutant virus by PolIY11-specific HLA-C*12:02-restricted T cells. Mass spectrometry-based immunopeptidome profiling of HIV-1-infected cells and analysis of crystal structures of TCR- and KIR2DL2-HLA-C*12:02-peptide complexes demonstrate the molecular basis for selection and recognition of the escape mutant epitope by TCR and KIR2DL2. The present study elucidates the mechanism for selection and inhibition of an HIV-1 escape virus by T cells and NK cells. HIV replication has been shown previously to be inhibited by combinations of T cells and NK cells according to HLA and KIR haplotype. Here the authors consider a combination of KIR2DL2+ NK and HLA-C*12:02-restricted T cells and clarify how a specific HIV pol escape mutant facilitates virus control by KIR2DL2+ NK cells.