The beta1 and beta3 integrins promote T cell receptor-mediated cytotoxic T lymphocyte activation

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 a...

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Bibliographic Details
Published in:The Journal of biological chemistry 2003-07, Vol.278 (29), p.26983-26991
Main Authors: Doucey, Marie-Agnès, Legler, Daniel F, Faroudi, Mustapha, Boucheron, Nicole, Baumgaertner, Petra, Naeher, Dieter, Cebecauer, Marek, Hudrisier, Denis, Rüegg, Curzio, Palmer, Ed, Valitutti, Salvatore, Bron, Claude, Luescher, Immanuel F
Format: Article
Language:English
Subjects:
Animals
Calcium Signaling
CD8 Antigens - metabolism
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 beta1 - 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
T-Lymphocytes, Cytotoxic - metabolism
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Summary: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.
ISSN:0021-9258