Abstract |
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-γ. Expression of NKG2D before the immature NK cell stage increased expression of the adaptor CD3ζ. Reduced expression of CD3ζ in Klrk1-/- mice was associated with enhanced signal transduction through NCR1, and CD3ζ 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.
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Authors | Vedrana Jelenčić, Marko Šestan, Inga Kavazović, Maja Lenartić, Sonja Marinović, Tim D Holmes, Michaela Prchal-Murphy, Berislav Lisnić, Veronika Sexl, Yenan T Bryceson, Felix M Wensveen, Bojan Polić |
Journal | Nature immunology
(Nat Immunol)
Vol. 19
Issue 10
Pg. 1083-1092
(10 2018)
ISSN: 1529-2916 [Electronic] United States |
PMID | 30224819
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, Ly
- Klrk1 protein, mouse
- NK Cell Lectin-Like Receptor Subfamily K
- Natural Cytotoxicity Triggering Receptor 1
- Ncr1 protein, mouse
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Topics |
- Animals
- Antigens, Ly
(immunology)
- Cytotoxicity, Immunologic
(immunology)
- Killer Cells, Natural
(immunology)
- Lymphocyte Activation
(immunology)
- Mice
- Mice, Knockout
- NK Cell Lectin-Like Receptor Subfamily K
(immunology)
- Natural Cytotoxicity Triggering Receptor 1
(immunology)
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