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 exami ned the in vitro biological properties of a panel of anti-human Fas mA b of IgG1 subclass (ZB4, VB3, WB3 and CBE), We found that anti-fas clo ne VB3 induced marked apoptotic cell death in Fas/APO-1-expressing Jur kat 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, efficient ly blocked apoptosis induced by CH-11. The WB3 and CBE clones neither induced or inhibited apoptosis, These antibodies were all found to rec ognize 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 relat ive affinity for the Fas/APO-1 molecule, These results provide further evidence for the potential of anti-fas antibodies of the IgG1 subclas s to elicit signals via the Fas/APO-1 molecule.