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 death when cross-linked with agonistic anti-Fas monoclonal antibodies (MAbs) or the endogenous Fas ligand. In this study, we investigated the in vitro biological properties of a panel of anti-human Fas MAbs. We found that five anti-Fas MAbs of IgG1 subclass (B.E28, B.G30, B.L25, DX2, and B.G34) induced marked apoptotic cell death in Fas-expressing leukemia cells, although this killing was delayed when compared to the cytolytic effect mediated by the 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 cell 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 for the Fas molecule. Furthermore, different clones recognized the same epitope and elicited different effects (induction or inhibition of cell killing); conversely, different clones elicited the same effect but recognized different epitopes. These results suggest that the different biological effects of anti-Fas MAbs would not be mediated in an epitope-restricted manner. The relative binding affinity might correlate to some extent with the biological properties of the MAb.
Komada
Y
Y
Department of Pediatrics, Mie University School of Medicine, Tsu, Japan. komada@clin.medic.mie-u.ac.jp
Inaba
H
H
Li
Q S
QS
Azuma
E
E
Zhou
Y W
YW
Yamamoto
H
H
Sakurai
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism; D000915:Antibody Affinity; D017209:Apoptosis / Q000276:immunology; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007938:Leukemia / Q000276:immunology / Q000473:pathology; D051379:Mice; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007074:Immunoglobulin G; D019014:fas Receptor