Heterosexual HIV-1 transmission is associated with allogeneic KIR/HLA ligand combinations governing natural killer cell alloreactivity

Wim Jennes, Sonja Verheyden, Christian Demanet, J.W. Mertens, C Camara, M Seydi, T Dieye, S Mboup, Luc Kestens

Onderzoeksoutput: Poster

Samenvatting

Killer-immunoglobin-like receptors (KIR) regulate natural killer (NK) cells in a human leukocyte antigen (HLA)-dependent manner. KIR/HLA gene combinations at the level of the individual influence susceptibility to HIV-1 acquisition and disease progression. Allogeneic KIR/HLA mismatches improve survival of leukaemia patients after hematopoietic stem cell transplantation. In this study, we analysed the effect of allogeneic KIR/ HLA mismatches on HIV-1 transmission in a West-African population of HIV-1 discordant and concordant couples. HIV-1 discordant couples were characterised by recipient partners with homozygous KIR2DL2, and by a mismatched recipient partner KIR2DL1/HLA-C2 index partner HLA-C1 combination expected to allow licensed missing self' NK cell killing of index partners' cells. HIV-1 concordant couples on the other hand were characterised 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 co-cultures of healthy donor-derived NK cells and HIV-1patient-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 HLA-1 transmission and that this may be due to recipient NK cell-mediated killing of the HIV-1 infected partner's cells.
Originele taal-2English
Pagina's39
Aantal pagina's1
StatusPublished - 2013
Evenement28th General Annual Meeting of the Belgian Hematological Society - Gent
Duur: 24 jan 201326 jan 2013

Other

Other28th General Annual Meeting of the Belgian Hematological Society
Periode24/01/1326/01/13

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