Anti-Fas IgG1 antibodies recognizing the same epitope of Fas/APO-1 mediate different biological effects in vitro

Fas/APO-1 is a cell surface glycoprotein that mediates programmed cell death or apoptosis when cross-linked with agonistic anti-fas or anti-APO-1 mAb or the endogenous Fas/APO-1 ligand, In this report, we examined the in vitro biological properties of a panel of anti-human Fas mAb of IgG1 subclass (ZB4, VB3, WB3 and CBE), We found that anti-fas clone VB3 induced marked apoptotic cell death in Fas/APO-1-expressing Jurkat cells, although this cell killing was delayed when compared to the cytolytic effect mediated by the prototypic anti-fas antibody of IgM subclass (clone CH-11), The ZB4 antibody, on the other hand, efficiently blocked apoptosis induced by CH-11. The WB3 and CBE clones neither induced or inhibited apoptosis, These antibodies were all found to recognize one and the same linear site on the Fas/APO-1 molecule, despite their different biological effects, The ability of these anti-fas mAb to induce or inhibit apoptosis appeared to correlate with their relative affinity for the Fas/APO-1 molecule, These results provide further evidence for the potential of anti-fas antibodies of the IgG1 subclass to elicit signals via the Fas/APO-1 molecule.