Engagement of CD160 receptor by HLA-C is a triggering mechanism used by circulating natural killer (NK) cells to mediate cytotoxicity

Philippe Le Bouteiller, Aliz Barakonyi, Jérome Giustiniani, Françoise Lenfant, Anne Marie-Cardine, Maryse Aguerre-Girr, Magali Rabot, Ivan Hilgert, Fathia Mami-Chouaib, Julie Tabiasco, Laurence Boumsell, Armand Bensussan

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98 Citations (Scopus)

Abstract

Circulating human natural killer (NK) lymphocytes have been functionally defined by their ability to exert cytotoxic activity against MHC class 1-negative target cell lines, including K562. Therefore, it was proposed that NK cells recognized the "missing self." We show here that the Ig-like CD160 receptor expressed by circulating CD56áim+ NK cells or IL-2-deprived NK cell lines is mainly involved in their cytotoxic activity against K562 target cells. Further, we report that HLA-C molecules that are constitutively expressed by K562 trigger NK cell lysis through CD160 receptor engagement. In addition, we demonstrate, with recombinant soluble HLA-Cw3 and CD160 proteins, direct interaction of these molecules. We also find that CD158b inhibitory receptors partially interfere with CD160-mediated cytotoxicity, whereas CD94/CD159a and CD85j have no effect on engagement with their respective ligands. Thus, CD160/HLA-C interaction constitutes a unique pathway to trigger NK cell cytotoxic activity.

Original languageEnglish
Pages (from-to)16963-16968
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number26
DOIs
Publication statusPublished - Dec 24 2002

Keywords

  • Activation
  • HLA class
  • NK receptors

ASJC Scopus subject areas

  • General

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    Le Bouteiller, P., Barakonyi, A., Giustiniani, J., Lenfant, F., Marie-Cardine, A., Aguerre-Girr, M., Rabot, M., Hilgert, I., Mami-Chouaib, F., Tabiasco, J., Boumsell, L., & Bensussan, A. (2002). Engagement of CD160 receptor by HLA-C is a triggering mechanism used by circulating natural killer (NK) cells to mediate cytotoxicity. Proceedings of the National Academy of Sciences of the United States of America, 99(26), 16963-16968. https://doi.org/10.1073/pnas.012681099