Abstract
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'.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Animals
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Antigens, CD / immunology*
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Cell Line, Tumor
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HeLa Cells
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Humans
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Immunity, Innate
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Intracellular Signaling Peptides and Proteins / immunology*
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Killer Cells, Natural / immunology*
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Lymphocyte Activation
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Melanoma, Experimental
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Mice
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Protein Tyrosine Phosphatase, Non-Receptor Type 6 / immunology*
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Receptors, Cell Surface / immunology*
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Signal Transduction
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Signaling Lymphocytic Activation Molecule Associated Protein
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Signaling Lymphocytic Activation Molecule Family
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Signaling Lymphocytic Activation Molecule Family Member 1
Substances
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Antigens, CD
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Intracellular Signaling Peptides and Proteins
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Receptors, Cell Surface
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SH2D1A protein, human
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SLAMF6 protein, human
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Sh2d1a protein, mouse
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Signaling Lymphocytic Activation Molecule Associated Protein
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Signaling Lymphocytic Activation Molecule Family
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Slamf6 protein, mouse
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Signaling Lymphocytic Activation Molecule Family Member 1
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Protein Tyrosine Phosphatase, Non-Receptor Type 6