NK cell killer Ig-like receptor repertoire acquisition and maturation are strongly modulated by HLA class i molecules

Marwan Sleiman, Nicolaas H.C. Brons, Tony Kaoma, Figen Dogu, Alexandra Villa-Forte, Patrick Lenoble, François Hentges, Katja Kotsch, Stephan D. Gadola, Carlos Vilches, Jacques Zimmer*

*Corresponding author for this work

    Research output: Contribution to journalArticleResearchpeer-review

    19 Citations (Scopus)


    The interaction between clonally distributed inhibitory receptors and their activating counterparts on NK cells and HLA class I molecules defines NK cell functions, but the role of HLA class I ligands in the acquisition of their receptors during NK development is still unclear. Although some studies demonstrated that HLA-C affects the expression of killer Ig-like receptors (KIR), other studies showed that NK cells acquire their KIR repertoire in a stochastic manner. Only when infected with human CMV is an expansion of self-specific KIR+ NKG2C+ NK cells detected. To gain more insight into this question, we compared the coexpression of different KIR molecules, NKG2A, CD8, and CD57, on NK cells in healthy donors and seven patients with deficient HLA class I expression due to mutations in one of the TAP genes. Our results show a correlation between the presence/absence of HLA class I molecules and the coexpression of their receptors. In an HLA class I low-expression context, an increase in KIR molecules' coexpression is detected on the NKG2A+ CD8+ subset. In functional assays, hyporesponsiveness was observed for TAPdeficient NK cells derived from four patients. In contrast, NK cells from patient five were functional, whereas CD107a+ and IFN-γ+ CD56dim NK cells presented a different pattern of HLA class I receptors compared with healthy donors. Taken together, our results provide strong evidence for the role of HLA class I molecules in NK cell maturation and KIR repertoire acquisition. The Journal of Immunology, 2014, 192: 2602-2610.

    Original languageEnglish
    Pages (from-to)2602-2610
    Number of pages9
    JournalJournal of Immunology
    Issue number6
    Publication statusPublished - 15 Mar 2014


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