Zeitschriftenaufsatz
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2018
NK cell receptor NKG2D sets activation threshold for the NCR1 receptor early in NK cell development
Autor:in
Jelenčić, Vedrana; Šestan, Marko; Kavazovic, Inga; Lenartic, Maja; Marinović, Sonja; Holmes, Tim D.; Prchal-Murphy, Michaela; Lisnic, Berislav; Sexl, Veronika; Bryceson, Yenan; Wensveen, Felix; Polic, Bojan
Publikationen als Autor:in / Herausgeber:in der Vetmeduni
Journal
Abstrakt
The activation of natural killer (NK) cells depends on a change in the balance of signals from inhibitory and activating receptors. The activation threshold values of NK cells are thought to be set by engagement of inhibitory receptors during development. Here, we found that the activating receptor NKG2D specifically set the activation threshold for the activating receptor NCR1 through a process that required the adaptor DAP12. As a result, NKGD2-deficient (Klrk1(-/-)) mice controlled tumors and cytomegalovirus infection better than wild-type controls through the NCR1-induced production of the cytokine IFN-gamma. Expression of NKG2D before the immature NK cell stage increased expression of the adaptor CD3 zeta. Reduced expression of CD3. in Klrk1(-/-) mice was associated with enhanced signal transduction through NCR1, and CD3. deficiency resulted in hyper-responsiveness to stimulation via NCR1. Thus, an activating receptor developmentally set the activity of another activating receptor on NK cells and determined NK cell reactivity to cellular threats.
Schlagwörter
Animals; Antigens, Lyimmunology; Cytotoxicity, Immunologicimmunology; Killer Cells, Naturalimmunology; Lymphocyte Activationimmunology; Mice; Mice, Knockout; NK Cell Lectin-Like Receptor Subfamily Kimmunology; Natural Cytotoxicity Triggering Receptor 1immunology
Dokumententyp
Originalarbeit
Open Access Type
Green
ISSN/eISSN
1529-2908 - 1529-2916
10.1038/s41590-018-0209-9
WoS ID
PubMed ID