title: Inhibitory KIR/HLA incompatibility between sexual partners confers protection against HIV-1 transmission.
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.
authors.affiliation: Laboratory of Immunology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium. wjennes@itg.be
authors.forename: Wim
authors.initials: W
authors.lastname: Jennes
authors.forename: Sonja
authors.initials: S
authors.lastname: Verheyden
authors.forename: Julie W
authors.initials: JW
authors.lastname: Mertens
authors.forename: Makhtar
authors.initials: M
authors.lastname: Camara
authors.forename: Moussa
authors.initials: M
authors.lastname: Seydi
authors.forename: Tandakha N
authors.initials: TN
authors.lastname: Dieye
authors.forename: Souleymane
authors.initials: S
authors.lastname: Mboup
authors.forename: Christian
authors.initials: C
authors.lastname: Demanet
authors.forename: Luc
authors.initials: L
authors.lastname: Kestens
mesh_terms: D000328:Adult; D000354:Africa, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D005260:Female; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control / Q000635:transmission*; D018023:HIV Seronegativity / Q000235:genetics / Q000276:immunology; D015497:HIV-1; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007519:Isoantigens / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008875:Middle Aged; D054340:Receptors, KIR / Q000235:genetics / Q000276:immunology*; D054343:Receptors, KIR2DL2 / Q000235:genetics / Q000276:immunology; D012747:Sexual Partners
chemical_list: D006680:HLA Antigens; D015236:HLA-C Antigens; D007519:Isoantigens; C515077:KIR2DL2 protein, human; D054340:Receptors, KIR; D054343:Receptors, KIR2DL2