Article: article from journal or magazin.
A role for the src family kinase Fyn in NK cell activation and the formation of the repertoire of Ly49 receptors.
European Journal of Immunology
NK cell function is regulated by a dual receptor system, which integrates signals from triggering receptors and MHC class I-specific inhibitory receptors. We show here that the src family kinase Fyn is required for efficient, NK cell-mediated lysis of target cells, which lack both self-MHC class I molecules and ligands for NKG2D, an activating NK cell receptor. In contrast, NK cell inhibition by the MHC class I-specific receptor Ly49A was independent of Fyn, suggesting that Fyn is specifically required for NK cell activation via non-MHC receptor(s). Compared to wild type, significantly fewer Fyn-deficient NK cells expressed the inhibitory Ly49A receptor. The presence of a transgenic Ly49A receptor together with its H-2(d) ligand strongly reduced the usage of endogenous Ly49 receptors in Fyn-deficient mice. These data suggest a model in which the repertoire of inhibitory Ly49 receptors is formed under the influenced of Fyn-dependent NK cell activation as well as the respective MHC class I environment. NK cells may acquire Ly49 receptors until they generate sufficient inhibitory signals to balance their activation levels. Such a process would ensure the induction of NK cell self-tolerance.
Animals, Antigens, Ly/biosynthesis, Antigens, Ly/immunology, CHO Cells, Carrier Proteins/biosynthesis, Carrier Proteins/immunology, Cricetinae, Cricetulus, Crosses, Genetic, Cytotoxicity, Immunologic, Enzyme Inhibitors/pharmacology, H-2 Antigens/immunology, Killer Cells, Lymphokine-Activated/immunology, Killer Cells, Natural/immunology, Lectins, C-Type, Lymphocyte Activation/physiology, Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/antagonists & inhibitors, Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/deficiency, Membrane Glycoproteins/biosynthesis, Membrane Glycoproteins/classification, Membrane Proteins/biosynthesis, Membrane Proteins/immunology, Mice, Mice, Inbred C57BL, Mice, Inbred Strains, Mice, Transgenic, NK Cell Lectin-Like Receptor Subfamily A, NK Cell Lectin-Like Receptor Subfamily K, Phosphorylation, Protein Processing, Post-Translational, Proto-Oncogene Proteins/antagonists & inhibitors, Proto-Oncogene Proteins/deficiency, Proto-Oncogene Proteins c-fyn, Pyrimidines/pharmacology, Receptors, Immunologic/biosynthesis, Receptors, Immunologic/immunology, Receptors, NK Cell Lectin-Like, Receptors, Natural Killer Cell, Recombinant Fusion Proteins/physiology, Self Tolerance/physiology, Tumor Cells, Cultured
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