B. Ybarrondo et al., CYTOTOXIC T-LYMPHOCYTE INTERACTION WITH FIBRONECTIN AND VITRONECTIN -ACTIVATED ADHESION AND COSIGNALING, Immunology, 91(2), 1997, pp. 186-192
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.