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

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 aWest 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.

Auteur(s) : Jennes W, Verheyden S, Mertens JW, Camara M, Seydi M, Dieye TN, Mboup S, Demanet C, Kestens L
Pages : 1157-64.
Année de publication : 2013
Revue : Blood
N° de volume : 121
Type : Article
Mise en ligne par : CAMARA Makhtar