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Scand J Immunol. 2017 Sep;86(3):135-142. doi: 10.1111/sji.12574.

The Abl-1 Kinase is Dispensable for NK Cell Inhibitory Signalling and is not Involved in Murine NK Cell Education.

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Center for Hematology and Regenerative Medicine (HERM), Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
Department of Medicine, Center for Infectious Medicine, F59, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Science for Life Laboratory, Department of Medicine Solna, Karolinska Institutet and Department of Neonatology, Karolinska Institutet and Department of Neonatology, Karolinska university Hospital, Stockholm, Sweden.
Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille UM2, INSERM, U1104, CNRS UMR 7258, Marseille, France.
Immunologie, Hôpital de la Conception, Assistance Publique - Hôpitaux de Marseille, Aix-Marseille Université, Marseille, France.
Department of Pediatrics and Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USA.


Natural killer (NK) cell responsiveness in the mouse is determined in an education process guided by inhibitory Ly49 and NKG2A receptors binding to MHC class I molecules. It has been proposed that inhibitory signalling in human NK cells involves Abl-1 (c-Abl)-mediated phosphorylation of Crk, lowering NK cell function via disruption of a signalling complex including C3G and c-Cbl, suggesting that NK cell education might involve c-Abl. Mice deficient in c-Abl expression specifically in murine NK cells displayed normal inhibitory and activating receptor repertoires. Furthermore, c-Abl-deficient NK cells fluxed Ca2+ normally after triggering of ITAM receptors, killed YAC-1 tumour cells efficiently and showed normal, or even slightly elevated, capacity to produce IFN-γ after activating receptor stimulation. Consistent with these results, c-Abl deficiency in NK cells did not affect NK cell inhibition via the receptors Ly49G2, Ly49A and NKG2A. We conclude that signalling downstream of murine inhibitory receptors does not involve c-Abl and that c-Abl plays no major role in NK cell education in the mouse.

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