title: Altered peptide ligands trigger perforin- rather than Fas-dependent cell lysis.
abstract: CTLs lyse Fas-expressing target cells by the concomitant action of a perforin- and a Fas-dependent mechanism. This study analyzed whether target cells pulsed with T cell antagonists and other altered peptide ligands (APLs) were susceptible selectively to only one of these two mechanisms. In vivo and in vitro activated T cells from transgenic mice expressing a TCR specific for lymphocytic choriomeningitis virus were used as effector cells. To distinguish between perforin- and Fas-dependent cytotoxicity, T cells from normal or perforin-deficient mice were used 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 demonstrate that target cells pulsed with T cell antagonists and other APLs are lysed predominantly by the perforin-dependent pathway. The contribution of Fas-mediated cytotoxicity was similar for the full agonist and the APLs. Thus, full agonists, partial agonists, and antagonists trigger similar and not distinct pathways of cytotoxicity.
authors.affiliation: Department of Medical Biophysics, Ontario Cancer Institute, Canada. bachmann@oci.utoronto.ca
authors.forename: M F
authors.initials: MF
authors.lastname: Bachmann
authors.forename: T
authors.initials: T
authors.lastname: Ohteki
authors.forename: K M
authors.initials: KM
authors.lastname: Faienza
authors.forename: A
authors.initials: A
authors.lastname: Zakarian
authors.forename: D
authors.initials: D
authors.lastname: Kägi
authors.forename: D E
authors.initials: DE
authors.lastname: Speiser
authors.forename: P S
authors.initials: PS
authors.lastname: Ohashi
mesh_terms: D000818:Animals; D016923:Cell Death / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology*
chemical_list: D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D011948:Receptors, Antigen, T-Cell; D019014:fas Receptor; D054353:Perforin