LCK-INDEPENDENT TRIGGERING OF T-CELL ANTIGEN RECEPTOR SIGNAL-TRANSDUCTION BY STAPHYLOCOCCAL ENTEROTOXINS

Superantigens (SAgs) activate T-cells in a manner specific to the V be ta region of the T-cell antigen receptor. Stimulations by SAgs provoke drastic T-cell activation that leads to programmed cell death or the anergic state of responding cells. To characterize the signal transduc tion pathway initiated by SAgs, mutant lines derived from the human le ukemic T-cell line Jurkat were tested for their reactivities against p rototypic SAgs, staphylococcal enterotoxins. The J.CaM1.6 cell line, w hich lacks Lck expression and lost reactivity against T-cell antigen r eceptor-mediated stimulation, was activated by staphylococcal enteroto xins in a manner indistinguishable from the Jurkat cell line. In contr ast, the J.45.01 cell line, which lacks expression of functional CD45, showed severely impaired reactivity. The role of Lck appears to be re placed by another Src family protein-tyrosine kinase, Fyn. In J.CaM1.6 cells, Fyn was rapidly phosphorylated and activated after staphylococ cal enterotoxin treatment. The kinase-inactive mutant of Fyn significa ntly suppressed the reactivity against staphylococcal enterotoxin E in J.CaM1.6 cells, and the expression of the active form of Fyn reconsti tuted reactivity against staphylococcal enterotoxin E in J.45.01 cells . These results demonstrate that SAgs activate T-cells in an Lck-indep endent pathway and that Fyn plays a critical role in the process.