NK cell receptor NKG2D sets activation threshold for the NCR1 receptor early in NK cell development
| Autor: | Veronika Sexl, Vedrana Jelenčić, Maja Lenartić, Michaela Prchal-Murphy, Yenan T. Bryceson, Tim D. Holmes, Berislav Lisnić, Marko Šestan, Inga Kavazović, Bojan Polić, Felix M. Wensveen, Sonja Marinović |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Cytotoxicity
Immunologic 0301 basic medicine medicine.medical_treatment Immunology Cell Stimulation Lymphocyte Activation Inhibitory postsynaptic potential Mice 03 medical and health sciences medicine Animals Antigens Ly Immunology and Allergy Receptor Mice Knockout Natural Cytotoxicity Triggering Receptor 1 Cell growth Chemistry BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences NKG2D Cell biology Killer Cells Natural 030104 developmental biology Cytokine medicine.anatomical_structure NK Cell Lectin-Like Receptor Subfamily K Signal transduction BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti NK cells NK cell education NKG2D NCR1 DAP12 CD3ζ CMV cancer immuno-surveillance |
| Zdroj: | Nature Immunology Volume 19 Issue 10 |
| ISSN: | 1529-2908 1529-2916 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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