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

• Published in: International immunology 1997-02, Vol.9 (2), p.201-209
• Main Authors: Fadeel, B, Thorpe, C J, Yonehara, S, Chiodi, F
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - pharmacology; Antibody Affinity; Apoptosis - drug effects; Apoptosis - immunology; Binding Sites - immunology; Cross Reactions; Epitope Mapping; Epitopes - immunology; Epitopes - metabolism; Epitopes - pharmacology; fas Receptor - drug effects; fas Receptor - immunology; fas Receptor - physiology; Humans; Immunoglobulin G - classification; Immunoglobulin G - metabolism; Immunoglobulin G - pharmacology; Jurkat Cells; Medicin och hälsovetenskap; Protein Binding - immunology
• ISSN: 0953-8178; 1460-2377; 1460-2377
• DOI: 10.1093/intimm/9.2.201

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.