Fibronectin induces phosphorylation of a 120-kDa protein and synergizes with the T cell receptor to activate cytotoxic T cell clones.
Fibronectin (FN) has been shown to act as a costimulator in both CD4+ and CD8+ T cell activation through the T cell receptor (TcR). Consistent with previous studies, we found that FN is able to both enhance the maximal amount of TcR-triggered degranulation and lower the threshold for activation. The density of immobilized anti-CD3 or anti-TcR required to induce degranulation and tyrosine phosphorylation of cellular proteins by several cytotoxic T lymphocyte clones is quantitatively about tenfold lower in the presence of FN. We further demonstrate that FN alone stimulates transient tyrosine phosphorylation of a 120-kDa protein (pp120) in CD8+ T cells and when FN is coimmobilized with substimulatory amounts of anti-CD3 or anti-TcR there is a synergistic response, resulting in prolonged and enhanced phosphorylation of pp120. To determine if FN acts as a costimulator in CD8+ cells solely through mediating adhesion events or if it also transduces signals in T cells we conducted remote stimulation experiments. Degranulation was induced when FN and sub-stimulatory anti-CD3 were presented on separate surfaces, indicating that FN induces independent transmembrane signals capable of augmenting TcR-induced signals resulting in a functional response. Both FN plus TcR-induced tyrosine phosphorylation of pp120 and degranulation are inhibited by RGD-containing peptides, implying that an RGD-dependent FN receptor is mediating phosphorylation of pp120 and enhancing TcR-mediated degranulation.
Department of Immunology, University of Alberta, Edmonton, Canada.
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D000595:Amino Acid Sequence; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D015550:Cell Degranulation / Q000276:immunology; D002999:Clone Cells; D005353:Fibronectins / Q000502:physiology*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D015151:Immunoblotting; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D017469:Receptors, Fibronectin / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015815:Cell Adhesion Molecules; D005353:Fibronectins; D009842:Oligopeptides; D011948:Receptors, Antigen, T-Cell; D017469:Receptors, Fibronectin; C047981:arginyl-glycyl-aspartic acid; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse