ALTERED PEPTIDE LIGANDS TRIGGER PERFORIN-DEPENDENT RATHER THAN FAS-DEPENDENT CELL-LYSIS

CTLs lyse Fas-expressing target cells by the concomitant action of a p erforin-and a Fas-dependent mechanism. This study analyzed whether tar get cells pulsed with T cell antagonists and other altered peptide lig ands (APLs) were susceptible selectively to only one of these two mech anisms. In vivo and in vitro activated T cells from transgenic mice ex pressing a TCR specific for lymphocytic choriomeningitis virus were us ed as effector cells. To distinguish between perforin- and Fas-depende nt cytotoxicity, T cells from normal or perforin-deficient mice were u sed to lyse peptide-pulsed Fas-positive or Fas-negative target cells. In contrast to previous reports that have shown that APLs selectively induce the Fas-dependent pathway of cytotoxicity, our results demonstr ate that target cells pulsed with T cell antagonists and other APLs ar e lysed predominantly by the perforin-dependent pathway, The contribut ion of Fas-mediated cytotoxicity was similar for the full agonist and the APLs. Thus, full agonists, partial agonists, and antagonists trigg er similar and not distinct pathways of cytotoxicity.