Title
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Impact of the variable killer Ig-like receptor-human leukocyte antigen interactions on natural killer cell cytotoxicity toward foreign CD4 T cells
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Author
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Abstract
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Background: Natural killer (NK) cells are known to mount a response against foreign target cells, where the absence of the dominant inhibitory killer Ig-like receptor (KIR)-human leukocyte antigen (HLA) interaction immensely lowers the threshold for NK cell activation. NK cells could thus constitute a vital part in the mucosal defense against cell-associated sexually transmitted diseases. Here, we performed a detailed analysis of hitherto unexplored KIR-HLA-incompatible NK cell interactions. Methods and findings: In vitro, healthy NK cells were cocultured with CD4+ T cells derived from human immunodeficiency virus-1 patients, and the KIR-specific NK cell cytotoxicity was measured using flow cytometry. Genotyping of KIR and HLA predicted the KIR-HLA interactions occurring during these 124 allogeneic encounters. KIR2DL1+ NK cells were seen as the strongest intrinsic responders in the absence of their ligand with a 3.2-fold increase in KIR2DL1+ NK cells in the total NK cell response. An association between the size of the alloreactive NK cell population and the amount of CD4+ T cell death (p = 0.0023) and NK cell degranulation (p = 0.0036) was only present in NK cell donors with an activating KIR haplotype. conclusion: We demonstrate differences in the activating effect of KIR-HLA incompatibility according to the KIR involved, with KIR2DL1 as the strongest responder. An activating KIR haplotype optimized the contribution of KIR-HLA-incompatible NK cells in the total NK cell response. |
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Language
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English
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Source (journal)
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Frontiers in immunology. - Place of publication unknown
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Publication
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Place of publication unknown
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2018
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ISSN
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1664-3224
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DOI
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10.3389/FIMMU.2018.01588
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Volume/pages
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9
(2018)
, 11 p.
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Article Reference
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1588
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ISI
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000437882800001
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Pubmed ID
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30038628
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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