title: HIV-1 Control by NK Cells via Reduced Interaction between KIR2DL2 and HLA-C∗12:02/C∗14:03.
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 virus-infected cells, providing additional understanding of NK cells in HIV-1 infection.
authors.affiliation: Center for AIDS Research, Kumamoto University, Chuo-ku, Kumamoto 860-0811, Japan.
authors.forename: Zhansong
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Kuroki
authors.affiliation: Center for AIDS Research, Kumamoto University, Chuo-ku, Kumamoto 860-0811, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Kuse
authors.affiliation: Center for AIDS Research, Kumamoto University, Chuo-ku, Kumamoto 860-0811, Japan.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Sun
authors.affiliation: Center for AIDS Research, Kumamoto University, Chuo-ku, Kumamoto 860-0811, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Akahoshi
authors.affiliation: Cancer and Inflammation Program, Laboratory of Experimental Immunology, Leidos Biomedical Research, Inc., Frederick National Laboratories for Cancer Research, Frederick, MD 21701, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Center for AIDS Research, Kumamoto University, Chuo-ku, Kumamoto 860-0811, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Chikata
authors.affiliation: Center for AIDS Research, Kumamoto University, Chuo-ku, Kumamoto 860-0811, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Naruto
authors.affiliation: Center for AIDS Research, Kumamoto University, Chuo-ku, Kumamoto 860-0811, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Koyanagi
authors.affiliation: Center for AIDS Research, Kumamoto University, Chuo-ku, Kumamoto 860-0811, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Murakoshi
authors.affiliation: Center for AIDS Research, Kumamoto University, Chuo-ku, Kumamoto 860-0811, Japan; AIDS Clinical Center, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Gatanaga
authors.affiliation: Center for AIDS Research, Kumamoto University, Chuo-ku, Kumamoto 860-0811, Japan; AIDS Clinical Center, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
authors.affiliation: Cancer and Inflammation Program, Laboratory of Experimental Immunology, Leidos Biomedical Research, Inc., Frederick National Laboratories for Cancer Research, Frederick, MD 21701, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139-3583, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.affiliation: Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Maenaka
authors.affiliation: Center for AIDS Research, Kumamoto University, Chuo-ku, Kumamoto 860-0811, Japan. Electronic address: masafumi@kumamoto-u.ac.jp.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takiguchi
mesh_terms: D000483:Alleles; D044466:Asian People; D002908:Chronic Disease; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D015236:HLA-C Antigens / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D054343:Receptors, KIR2DL2 / Q000378:metabolism*; D019562:Viral Load; D014779:Virus Replication
chemical_list: D015236:HLA-C Antigens; C515077:KIR2DL2 protein, human; D054343:Receptors, KIR2DL2
keywords: HIV-1; HLA-C; KIR2DL2; NK cells