Molecular basis for selection and inhibition of HIV-1 escape virus by T cells and KIR2DL2+NK cells
NK cells and CD8<sup>+</sup> 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<sup>+</sup> T cells and NK cells recognizing superimposed Pol peptides in selection and control of HIV-1 mutant virus. KIR2DL2<sup>+</sup>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.
Authors
- Kimiko Kuroki (ORCID: https://orcid.org/0000-0001-9796-4217)
- Aure Aflalo (ORCID: https://orcid.org/0000-0002-7158-6868)
- Wayne Paes (ORCID: https://orcid.org/0000-0002-0529-2765)
- Persephone Borrow (ORCID: https://orcid.org/0000-0002-3877-9780)
- Zhansong Lin
- Robert Parker (ORCID: https://orcid.org/0000-0002-6578-7401)
- Hiroyuki Gatanaga (ORCID: https://orcid.org/0000-0001-9191-9984)
- Haruki Matsubara (ORCID: https://orcid.org/0000-0001-6226-8617)
- Shinichi Oka (ORCID: https://orcid.org/0000-0001-7481-9009)
- Hiroki Kusaka
- Takayuki Chikata (ORCID: https://orcid.org/0000-0001-8907-1320)
- Katsumi Maenaka (ORCID: https://orcid.org/0000-0002-5459-521X)
- Ryuma Sakata
- Anna E. Kliszczak
- Annalisa Nicastri (ORCID: https://orcid.org/0000-0002-1895-0317)
- Toyoyuki Ose (ORCID: https://orcid.org/0000-0002-2001-9388)
- Nobumoto Tomioka (ORCID: https://orcid.org/0000-0001-6751-416X)
- Nozomi Kuse (ORCID: https://orcid.org/0000-0003-3852-2288)
- Masafumi Takiguchi (ORCID: https://orcid.org/0000-0002-8516-6442)
- Shunsuke Kita (ORCID: https://orcid.org/0000-0003-3969-302X)
- Ryoya Yamashita
- Nicola Ternette (ORCID: https://orcid.org/0000-0002-9283-0743)
- Yu Zhang (ORCID: https://orcid.org/0000-0002-5446-5650)
- Yosuke Watanabe
- Tomohiro Akahoshi
Institutions
- Hokkaido University of Science (JP)
- Kyushu University (JP)
- Kumamoto Health Science University (JP)
- Hokkaido University (JP)
- Hokkaido Pharmaceutical University (JP)
- University of Oxford (GB)
- National Center for Global Health and Medicine (JP)
- Kumamoto University (JP)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-11-06
- DOI
- https://doi.org/10.1038/s41467-025-64768-2
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Japan Agency for Medical Research and Development
- Ministry of Education, Culture, Sports, Science and Technology
- Hokkaido University
- National Institutes of Health
- Japan Society for the Promotion of Science
- National Institute of Allergy and Infectious Diseases