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Quantity of HLA-C surface expression and licensing of KIR2DL+ natural killer cells

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Abstract

Natural killer (NK) cells require interaction of inhibitory surface receptors with human leukocyte antigen (HLA) ligands during development to acquire functional competence in a process termed “licensing.” The quantity of HLA required for this process is unknown. Two polymorphisms affecting HLA-C surface expression (rs9264942 and rs67384697) have recently been identified, and shown to influence progression of HIV infection. We typed a cohort of healthy donors for the two HLA-C-related polymorphisms, KIR2DL1 and KIR2DL3, and their respective HLA-C ligands and analyzed how HLA ligands influenced licensing status of killer cell immunoglobulin-like receptor (KIR)+ NK cells in terms of degranulation and cytokine production in response to HLA-deficient target cells. The presence of respective HLA class I ligands increased the function of KIR2DL1+ and KIR2DL3+ NK cells in a dose-dependent manner. In contrast, neither of the HLA-C-related polymorphisms nor the quantity of cell surface HLA-C had any significant effect on NK cell function. Interestingly, HLA-Cw7—an HLA-C allele with low surface expression—licensed KIR2DL3+ NK cells more strongly than any other KIR2DL3 ligand. The quantity of cell surface HLA-C does not appear to influence licensing of NK cells, and the HLA-C-related polymorphisms presumably influence HIV progression through factors unrelated to NK cell education.

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Acknowledgments

This study was supported by grants from the Swiss National Science Foundation (grant PPOOP3_128461/1) and by the "Novartis Stiftung für medizinisch-biologische Forschung."

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Correspondence to Martin Stern.

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Charoudeh, H.N., Schmied, L., Gonzalez, A. et al. Quantity of HLA-C surface expression and licensing of KIR2DL+ natural killer cells. Immunogenetics 64, 739–745 (2012). https://doi.org/10.1007/s00251-012-0633-1

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  • DOI: https://doi.org/10.1007/s00251-012-0633-1

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