Mapping of the linear site on the Fas/APO-1 molecule targeted by the prototypic anti-Fas mAb.
Fas/APO-1 is a member of the nerve growth factor/tumor necrosis factor (TNF) family of receptors and has been shown to mediate apoptotic cell death upon binding of specific mAb. We report here that the prototypic anti-human Fas mAb (clone CH-11) induces apoptosis by binding to a linear epitope present on the extracellular domain of the Fas/APO-1 protein. Synthetic peptides corresponding to this epitope blocked the apoptotic effect of the antibody in a susceptible Jurkat T cell line. Based upon the similarity between the Fas/APO-1 protein and the recently crystallized soluble TNF receptor type I, we generated a molecular model of Fas/APO-1, Our computer modeling indicates that the antibody binding region forms a hairpin loop on the surface of the Fas/ APO-1 protein. These findings further our understanding of the Fas/APO-1-mediated apoptotic signal and may provide a useful tool in future investigations of programmed cell death.
Fadeel
B
B
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden.
Thorpe
J
J
Chiodi
F
F
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D017209:Apoptosis / Q000276:immunology; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D003198:Computer Simulation; D018604:Epitope Mapping; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D013601:T-Lymphocytes / Q000276:immunology; D019014:fas Receptor / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
D000911:Antibodies, Monoclonal; D019014:fas Receptor