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Nat Immunol. 2016 Apr;17(4):387-96. doi: 10.1038/ni.3369. Epub 2016 Feb 15.

A hematopoietic cell-driven mechanism involving SLAMF6 receptor, SAP adaptors and SHP-1 phosphatase regulates NK cell education.

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Laboratory of Molecular Oncology, Institut de recherches cliniques de Montréal (IRCM), Montréal, Québec, Canada.
Department of Medicine, University of Montréal, Montréal, Québec, Canada.
Department of Medicine, McGill University, Montréal, Québec, Canada.
Laboratory of Lymphocyte Activation and Susceptibility to EBV, Université Paris Descartes Sorbonne Paris Cité, Institut Imagine, Paris, France.


Activation of natural killer (NK) cells by hematopoietic target cells is controlled by the SLAM family of receptors and by the associated SAP family of adaptors. Here we found that SLAM receptors also enhanced NK cell activation by nonhematopoietic target cells, which lack ligands for SLAM receptors. This function was mediated by SLAMF6, a homotypic SLAM receptor found on NK cells and other hematopoietic cells, and was regulated by SAP adaptors, which uncoupled SLAM receptors from phosphatase SHP-1 and diminished the effect of SLAMF6 on NK cell responsiveness toward nonhematopoietic cells. Thus, in addition to their role in NK cell activation by hematopoietic cells, the SLAM-SAP pathways influence responsiveness toward nonhematopoietic targets by a process akin to NK cell 'education'.

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