| Abstract: | 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. |
