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.

journal_name

Blood

journal_title

Blood

authors

Jennes W,Verheyden S,Mertens JW,Camara M,Seydi M,Dieye TN,Mboup S,Demanet C,Kestens L

doi

10.1182/blood-2012-09-455352

subject

Has Abstract

pub_date

2013-02-14 00:00:00

pages

1157-64

issue

7

eissn

0006-4971

issn

1528-0020

pii

blood-2012-09-455352

journal_volume

121

pub_type

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