B. Fadeel et al., MAPPING OF THE LINEAR SITE ON THE FAS APO-1 MOLECULE TARGETED BY THE PROTOTYPIC ANTI-FAS MAB/, International immunology, 7(12), 1995, pp. 1967-1975
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 cel
l death upon binding of specific mAb. We report here that the prototyp
ic 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 pr
otein. Synthetic peptides corresponding to this epitope blocked the ap
optotic effect of the antibody in a susceptible Jurkat T cell line. Ba
sed upon the similarity between the Fas/APO-1 protein and the recently
crystallized soluble TNF receptor type I, we generated a molecular mo
del of Fas/APO-1. Our computer modeling indicates that the antibody bi
nding region forms a hairpin loop on the surface of the Fas/APO-1 prot
ein. These findings further our understanding of the Fas/APO-1-mediate
d apoptotic signal and may provide a useful tool in future investigati
ons of programmed cell death.