CYTOTOXIC T-LYMPHOCYTE INTERACTION WITH FIBRONECTIN AND VITRONECTIN -ACTIVATED ADHESION AND COSIGNALING

Stimulation of cloned cytotoxic T lymphocytes (CTL) with anti-T-cell r eceptor (TCR) monoclonal antibody (mAb) in solution resulted in rapid and sustained activation of adhesion to immobilized fibronectin (FN bu t did not initiate degranulation. Addition of a second antibody (Ab) t o further cross-link the TCR substantially increased the level of adhe sion and also activated degranulation, as measured by release of serin e esterase? in the presence of immobilized FN but not in its absence. Thus, binding to FN can provide a costimulatory signal to activate deg ranulation, TCR cross-linking also activated CDS-dependent adhesion to class I, and CD8 provided a costimulatory signal upon binding to clas s I. However, the requirements for activating adhesion and generating the costimulatory signal differed significantly for FN versus class I ligand, suggesting that these two receptor-ligand systems do not share a common mechanism of action. Co-immobilizing FN and alloantigen resu lted in increased serine esterase release in comparison with that stim ulated by antigen alone, and required the FN and class I be on the sam e surface. Peptide and antibody blocking demonstrated that CTL binding to FN, and to vitronectin (VN), was mediated by the alpha V beta(3) v itronectin receptor (VNR). Thus, VNR is activated by a signal from the TCR to mediate adhesion to FN or VN, and delivers a costimulatory sig nal for degranulation via a different mechanism than costimulation by CD8 binding to class I.