Article: article from journal or magazin.
The beta1 and beta3 integrins promote T cell receptor-mediated cytotoxic T lymphocyte activation.
Journal of Biological Chemistry
Recognition by CD8+ cytotoxic T lymphocytes (CTLs) of antigenic peptides bound to major histocompatibility class (MHC) I molecules on target cells leads to sustained calcium mobilization and CTL degranulation resulting in perforin-dependent killing. We report that beta1 and beta3 integrin-mediated adhesion to extracellular matrix proteins on target cells and/or surfaces dramatically promotes CTL degranulation. CTLs, when adhered to fibronectin but not CTL in suspension, efficiently degranulate upon exposure to soluble MHC.peptide complexes, even monomeric ones. This adhesion induces recruitment and activation of the focal adhesion kinase Pyk2, the cytoskeleton linker paxillin, and the Src kinases Lck and Fyn in the contact site. The T cell receptor, by association with Pyk2, becomes part of this adhesion-induced activation cluster, which greatly increases its signaling.
Animals, Antigens, CD29/metabolism, Antigens, CD8/metabolism, Calcium Signaling, Cell Adhesion, Cell Degranulation, Cell Line, Cytoskeletal Proteins/metabolism, Cytotoxicity, Immunologic, Fibronectins/metabolism, Focal Adhesion Kinase 2, H-2 Antigens/genetics, H-2 Antigens/metabolism, Integrin beta3/metabolism, Lymphocyte Activation, Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/metabolism, Mice, Paxillin, Phosphoproteins/metabolism, Protein-Tyrosine Kinases/metabolism, Proto-Oncogene Proteins/metabolism, Proto-Oncogene Proteins c-fyn, Receptor-CD3 Complex, Antigen, T-Cell/metabolism, Receptors, Antigen, T-Cell/metabolism, Signal Transduction, T-Lymphocytes, Cytotoxic/cytology, T-Lymphocytes, Cytotoxic/immunology
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