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.
Fadeel
B
B
Microbiology and Tumorbiology Center, Karolinska Institutet, Stockholm, Sweden.
Thorpe
C J
CJ
Yonehara
S
S
Chiodi
F
F
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology; D000915:Antibody Affinity; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001665:Binding Sites / Q000276:immunology; D003429:Cross Reactions; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000145:classification / Q000378:metabolism / Q000494:pharmacology*; D019169:Jurkat Cells; D011485:Protein Binding / Q000276:immunology; D019014:fas Receptor / Q000187:drug effects / Q000276:immunology* / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007074:Immunoglobulin G; D019014:fas Receptor