ACTIVATED ADHESION OF CTL TO MHC CLASS-I BUT NOT TO FIBRONECTIN IS INHIBITED BY CIS-UNSATURATED FATTY-ACIDS AND PHENYLARSINE OXIDE

Binding of CTL to MHC class I or fibronectin is activated through TCR signaling. Once activated, CTL adhesion to MHC class I results in tyro sine phosphorylation of CTL substrates, phosphatidylinositol (Pl) turn over, and degranulation, Although activated adhesion to fibronectin do es not itself initiate Pl hydrolysis or degranulation, these responses are amplified once they become activated. In the present study we hav e examined the effect of cis unsaturated fatty acids (FA) and phenylar sine oxide (PAO) on CD8-mediated adhesion of CTL to immobilized class I protein and on biochemical and functional events that are triggered by this adhesion. Previous studies have shown that FA and low concentr ations of PAO inhibit specific tyrosine phosphorylation events and deg ranulation but have no effect on Pl turnover or CTL-target cell conjug ates. The present results show that pretreating CTL with cis unsaturat ed, but not saturated, FA and low concentrations of PAO (< 0.5 mu M) i nhibit soluble anti-TCR-triggered binding of CD8 to immobilized MHC cl ass I, tyrosine phosphorylation of CTL substrates, Pl turnover, and de granulation, Addition of cis unsaturated FA or PAO after CTL have been allowed to bind to immobilized class I protein did not affect the lev el of adhesion, In contrast, neither cis unsaturated FA nor PAO affect ed the TCR-activated binding of CTL to fibronectin. These results sugg est that activation of adhesion to the class I and fibronectin ligands involves divergent different pathways that can be distinguished by th e FA and PAO agents.