Inhibitory KIR/HLA incompatibility between sexual partners confers protection against HIV-1 transmission

Blood. 2013 Feb 14;121(7):1157-64. doi: 10.1182/blood-2012-09-455352. Epub 2012 Dec 13.

Abstract

Killer immunoglobulin-like receptors (KIRs) regulate natural killer (NK) cells in a human leukocyte antigen (HLA)-dependent manner. KIR/HLA mismatched hematopoietic stem cell transplants induce alloreactive NK cells, which prevent leukemia relapse. Certain KIR/HLA combinations protect against HIV-1 infection, but the effect of KIR/HLA mismatches between sexual partners has never been investigated. In this study, we analyzed the effect of allogeneic KIR/HLA combinations on HIV-1 transmission in a West African population of HIV-1-discordant and concordant couples. HIV-1-discordant couples were characterized by recipient partners with homozygous KIR2DL2, and by a mismatched recipient partner KIR2DL1/HLA-C2 with index partner HLA-C1/C1 combination expected to allow licensed missing self NK cell killing of index partners' cells. HIV-1-concordant couples on the other hand were characterized by KIR2DL3 homozygous recipient partners with HLA-C1/C2 bearing index partners, resulting in a matched KIR/HLA combination expected to inhibit NK cell killing. In vitro cocultures of healthy donor-derived NK cells and HIV-1 patient-derived CD4(+) T cells confirmed the involvement of these allogeneic KIR/HLA combinations in NK cell-mediated CD4(+) T-cell killing. Our data suggest that KIR/HLA incompatibility between sexual partners confers protection against HIV-1 transmission and that this may be due to alloreactive NK cell killing of the HIV-1-infected partner's cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Africa, Western
  • CD4-Positive T-Lymphocytes / immunology
  • Coculture Techniques
  • Cytotoxicity, Immunologic
  • Female
  • HIV Infections / genetics
  • HIV Infections / immunology*
  • HIV Infections / prevention & control
  • HIV Infections / transmission*
  • HIV Seronegativity / genetics
  • HIV Seronegativity / immunology
  • HIV-1*
  • HLA Antigens / genetics
  • HLA Antigens / immunology*
  • HLA-C Antigens / genetics
  • HLA-C Antigens / immunology
  • Humans
  • Immunity, Innate
  • Isoantigens / genetics
  • Isoantigens / immunology
  • Killer Cells, Natural / immunology
  • Male
  • Middle Aged
  • Receptors, KIR / genetics
  • Receptors, KIR / immunology*
  • Receptors, KIR2DL2 / genetics
  • Receptors, KIR2DL2 / immunology
  • Sexual Partners

Substances

  • HLA Antigens
  • HLA-C Antigens
  • Isoantigens
  • KIR2DL2 protein, human
  • Receptors, KIR
  • Receptors, KIR2DL2