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Title
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Inhibitory KIR/HLA incompatibility between sexual partners confers protection against HIV-1 transmission
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Author
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Abstract
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| 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-1discordant and concordant couples. HIV-1discordant 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-1concordant 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 cellmediated 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-1infected partner's cells. |
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Language
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English
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Source (journal)
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Blood / American Society of Hematology. - New York, N.Y.
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Publication
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New York, N.Y.
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2013
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ISSN
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0006-4971
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DOI
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10.1182/BLOOD-2012-09-455352
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Volume/pages
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121
:7
(2013)
, p. 1157-1164
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ISI
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000314870700019
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Full text (Publisher's DOI)
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