A role for the src family kinase Fyn in NK cell activation and the formation of the repertoire of Ly49 receptors.
- Lowin-Kropf B Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland.
- Kunz B
- Schneider P
- Held W
- 2002-03-01
Published in:
- 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
English
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.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1002/1521-4141(200203)32:3<773::AID-IMMU773>3.0.CO;2-U
- PMID 11870621
- Persistent URL
- https://sonar.ch/global/documents/93581
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