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PELs and the Perforin and Granzyme Independent Mechanism of CTL‐mediated Lysis
Author(s) -
BERKE GIDEON
Publication year - 1995
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.1995.tb00681.x
Subject(s) - perforin , granzyme , ctl* , lytic cycle , fas ligand , microbiology and biotechnology , biology , intracellular , granzyme b , cytolysin , granzyme a , apoptosis , programmed cell death , immunology , t cell , immune system , biochemistry , cd8 , virus , virulence , gene
The central role of CTLs in immunopathology accounts for the increasing interest in deciphering the mechanism whereby they kill at the molecular level. Recent studies show that CTLs have two molecularly distinct lytic mechanisms at their disposal. The first involves the direct effect(s) of the pore-forming protein perforin, possibly in conjunction with granzymes. In recent years, experiments conducted in our laboratory led to an alternative pathway, of receptor-mediated mechanism for CTL killing, involving neither the secretion nor the lytic action of the pore-forming protein perforin or of granzymes. By this mechanism, engagement of a CTL membrane ligand and an apoptosis-inducing target cell surface receptor triggers the disintegration of the CTL-bound target cell. Cross-linking of apoptosis-inducing target cell surface molecules (e.g. Fas), induced upon binding of CTL ligands (e.g. Fas-L), may be required and sufficient to trigger target cell apoptosis. Intracellular lethal signals emanating from the cross-linked intracellular death domain of Fas are postulated.