title: TCR antagonist peptides induce formation of APC-T cell conjugates and activate a Rac signaling pathway.
abstract: T cell receptor antagonists inhibit T cell activation by antigen, and by themselves fail to induce phenotypic changes associated with T cell activation. However, they can induce limited tyrosine phosphorylation of TCRzeta chain. Here we show that TCR antagonists are potent inducers of APC-T cell conjugates, cytoskeletal reorganization, and capping of certain T cell proteins. These events are associated with a signaling pathway involving tyrosine phosphorylation of Vav and SLP-76, activation and capping of Rac-1, a protein previously linked with cytoskeletal reorganization, and activation of JNK. The finding that antagonist peptides stimulate this pathway, while failing to stimulate other TCR-mediated signaling pathways, indicates the presence in T cells of a hierarchy of signaling that is sensitive to the avidity of Ag / MHC-TCR interaction.
authors.affiliation: La Jolla Institute for Allergy and Immunology, San Diego, USA.
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.forename: K
authors.initials: K
authors.lastname: Sugie
authors.forename: D M
authors.initials: DM
authors.lastname: La Face
authors.forename: A
authors.initials: A
authors.lastname: Altman
authors.forename: H M
authors.initials: HM
authors.lastname: Grey
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology*; D018797:Cell Cycle Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051567:Proto-Oncogene Proteins c-vav; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors* / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell; C092947:SLP-76 signal Transducing adaptor proteins; C496619:Vav1 protein, mouse; D014443:Tyrosine; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D016283:Proto-Oncogene Proteins p21(ras); D020744:rac GTP-Binding Proteins