Altered peptide ligands trigger perforin- rather than Fas-dependent cell lysis.

Journal article

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: Bachmann, M; Ohteki, T; Faienza, K; Zakarian, A; Kägi, D

• Publication status: Published
• Journal: Journal of Immunology
• Volume: 159
• Issue: 9
• Pages: 4165-4170
• Publication date: 1997-11-01
• EISSN: 1550-6606
• ISSN: 0022-1767
• Language: English
• Keywords: Membrane Glycoproteins; Pore Forming Cytotoxic Proteins; Perforin; Cytotoxicity, Immunologic; T-Lymphocytes, Cytotoxic; Receptors, Antigen, T-Cell; Antigens, CD95; Mice; Animals; Cell Death; Fas Ligand Protein; Mice, Transgenic