Lowin-Kropf B Kunz B Schneider P Held W 2002 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. application/pdf https://sonar.ch/global/documents/93581 eng info:eu-repo/semantics/altIdentifier/doi/10.1002/1521-4141(200203)32:3<773::AID-IMMU773>3.0.CO;2-U info:eu-repo/semantics/altIdentifier/pmid/11870621 info:eu-repo/semantics/openAccess European journal of immunology. - 2002 Animals Antigens, Ly CHO Cells Carrier Proteins Cricetinae Cricetulus Crosses, Genetic Cytotoxicity, Immunologic Enzyme Inhibitors H-2 Antigens Histocompatibility Antigen H-2D Killer Cells, Lymphokine-Activated Killer Cells, Natural Lectins, C-Type Lymphocyte Activation Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Membrane Glycoproteins Membrane Proteins 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 Proto-Oncogene Proteins c-fyn Pyrimidines Receptors, Immunologic Receptors, NK Cell Lectin-Like Receptors, Natural Killer Cell Recombinant Fusion Proteins Self Tolerance Tumor Cells, Cultured A role for the src family kinase Fyn in NK cell activation and the formation of the repertoire of Ly49 receptors. http://purl.org/coar/resource_type/c_6501