title: The beta1 and beta3 integrins promote T cell receptor-mediated cytotoxic T lymphocyte activation.
abstract: 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.
authors.affiliation: Institute for Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland. ma_doucey@hotmail.com
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Doucey
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Legler
authors.forename: Mustapha
authors.initials: M
authors.lastname: Faroudi
authors.forename: Nicole
authors.initials: N
authors.lastname: Boucheron
authors.forename: Petra
authors.initials: P
authors.lastname: Baumgaertner
authors.forename: Dieter
authors.initials: D
authors.lastname: Naeher
authors.forename: Marek
authors.initials: M
authors.lastname: Cebecauer
authors.forename: Denis
authors.initials: D
authors.lastname: Hudrisier
authors.forename: Curzio
authors.initials: C
authors.lastname: Rüegg
authors.forename: Ed
authors.initials: E
authors.lastname: Palmer
authors.forename: Salvatore
authors.initials: S
authors.lastname: Valitutti
authors.forename: Claude
authors.initials: C
authors.lastname: Bron
authors.forename: Immanuel F
authors.initials: IF
authors.lastname: Luescher
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000378:metabolism; D020013:Calcium Signaling; D002448:Cell Adhesion; D015550:Cell Degranulation; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D005353:Fibronectins / Q000378:metabolism; D051418:Focal Adhesion Kinase 2; D006183:H-2 Antigens / Q000235:genetics / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism*; D039661:Integrin beta3 / Q000378:metabolism*; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D051379:Mice; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D016827:CD8 Antigens; D003598:Cytoskeletal Proteins; D005353:Fibronectins; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D019012:Integrin beta1; D039661:Integrin beta3; D051419:Paxillin; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; C496062:Pxn protein, mouse; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2; C494960:Fyn protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; C496053:Ptk2b protein, mouse