Epitopes and functional responses defined by a panel of anti-Fas (CD95) monoclonal antibodies

Fas (CD95) is a cell surface glycoprotein that mediates apoptotic cell deat h when cross-linked with agonistic anti-Fas monoclonal antibodies (MAbs) or the endogenous Fas ligand, In this study, we investigated the in vitro bio logical properties of a panel of anti-human Fas MAbs, We found that five an ti-Fas MAbs of IgG(1) subclass (B.E28, B.G30, B.L25, DX2, and B.G34) induce d marked apoptotic cell death in Fas-expressing leukemia cells, although th is killing was delayed when compared to the cytolytic effect mediated by th e prototypic anti-Fas MAb of IgM subclass (clone CH-11). On the other hand, four clones (ZB4, B.G27, B.D29, and B.K14) efficiently blocked apoptotic c ell death induced by the CH-11 MAb or Fas ligand, The ability of these MAbs to inhibit cell death appeared to correlate with their relative affinity f or the Fas molecule, Furthermore, different clones recognized the same epit ope and elicited different effects (induction or inhibition of cell killing ); conversely, different clones elicited the same effect but recognized dif ferent epitopes, These results suggest that the different biological effect s of anti-Fas MAbs would not be mediated in an epitope-restricted manner. T he relative binding affinity might correlate to some extent with the biolog ical properties of the MAb.