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HIV-1 Control by NK Cells via Reduced Interaction between KIR2DL2 and HLA-C*12:02/C*14:03

  1. Author:
    Lin, Zhansong
    Kuroki, Kimiko
    Kuse, Nozomi
    Sun, Xiaoming
    Akahoshi, Tomohiro
    Qi, Ying
    Chikata, Takayuki
    Naruto, Takuya
    Koyanagi, Madoka
    Murakoshi, Hayato
    Gatanaga, Hiroyuki
    Oka, Shinichi
    Carrington, Mary
    Maenaka, Katsumi
    Takiguchi, Masafumi

  2. Author Address

    Kumamoto Univ, Ctr AIDS Res, Chuo Ku, Kumamoto 8600811, Japan.Hokkaido Univ, Fac Pharmaceut Sci, Lab Biomol Sci, Kita Ku, Sapporo, Hokkaido 0600812, Japan.Leidos Biomed Res Inc, Frederick Natl Labs Canc Res, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21701 USA.MIT, MGH, Ragon Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA.Harvard, Cambridge, MA 02139 USA.Natl Ctr Global Hlth & Med, AIDS Clin Ctr, Shinjuku Ku, Tokyo 1628655, Japan.
    1. Year: 2016
    2. Date: Nov 22
  2. Journal: CELL REPORTS
  3. CELL PRESS,
    1. 17
    2. 9
    3. Pages: 2210-2220
  5. Type of Article: Article
  6. ISSN: 2211-1247
  1. Abstract:

    Natural killer (NK) cells control viral infection in part through the interaction between killer cell immunoglobulin-like receptors (KIRs) and their human leukocyte antigen (HLA) ligands. We investigated 504 anti-retroviral (ART)-free Japanese patients chronically infected with HIV-1 and identified two KIR/HLA combinations, KIR2DL2/HLA-C*12:02 and KIR2DL2/HLA-C*14:03, that impact suppression of HIV-1 replication. KIR2DL2(+) NK cells suppressed viral replication in HLA-C*14:03(+) or HLA-C*12:02(+) cells to a significantly greater extent than did KIR2DL2(-) NK cells in vitro. Functional analysis showed that the binding between HIV-1-derived peptide and HLA-C*14:03 or HLA-C*12:02 influenced KIR2DL2(+) NK cell activity through reduced expression of the peptide-HLA (pHLA) complex on the cell surface (i.e., reduced KIR2DL2 ligand expression), rather than through reduced binding affinity of KIR2DL2 to the respective pHLA complexes. Thus, KIR2DL2/HLA-C*12:02 and KIR2DL2/HLA-C*14:03 compound genotypes have protective effects on control of HIV-1 through a mechanism involving KIR2DL2-mediated NK cell recognition of virusinfected cells, providing additional understanding of NK cells in HIV-1 infection.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.celrep.2016.10.075
  3. PMID: 27880898
  4. View record in Web of Science®
  5. WOS: 000390893600005

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