Hello all:

In 1984, Shin Yonehara, Ai Ishii and Minako Yonehara established anti-Fas monoclonal antibody (CH-11) with associated cell killing activity (Reference 1), when Yonehara et al. tried to prepare monoclonal antibodies against cell surface receptor for human type I interferon (IFN). This research project has been carried out in the Tokyo Metropolitan Institute for Medical Science, Tokyo, Japan.

Hybridoma cells producing monoclonal antibodies were prepared by using the spleen cells of mice immunized with human diploid fibroblast FS-7 cells. The supernatants of the hybridomas were screened for neutralizing the antiviral activity of IFN. That is, human amnion-derived FL cells were treated with IFN in the presence of the supernatant of hybridomas followed by the infection of RNA virus VSV. Viral growth was measured by either the cytopatheic effect (cell-killing effect by virus) or the incorporation of tritiated uridine into viral RNA in the presence of actinomycin D, an inhibitor of cellular RNA synthesis. One supernatant gave interesting results: the cytopatheic effect was not inhibited even in the presence of IFN although the incorporation of uridine was entirely inhibited either in the presence or absence of IFN. The supernatant seemed to neutralize the antiviral activity of IFN in the cytopatheic effect but not in the viral RNA synthesis. Finally, control experiments in the absence of virus or actinomycin D clearly showed that monoclonal antibody in the supernatant directly kill FL cells in the presence of actinomycin D (Now it is well known that Fas-mediated apoptosis-inducing signal is enhanced by the treatment of cells with actinomycin D).

Shin Yonehara designated the antigen recognized by the monoclonal antibody as Fas antigen. The first meaning of Fas antigen is FS-7 (F)- and FL (F)-associated (a) cell surface (s) antigen.

In 1988, Shin Yonehara asked Shigekazu Nagata to start the cDNA cloning of human Fas antigen in collaboration. In 1991, we succeeded in the cDNA cloning and Fas antigen was shown to be a member of the TNF receptor family (reference 2). Since mouse cell transformants expressing human Fas antigen undergo apoptosis by anti-human Fas antibody, we concluded that Fas antigen can transduce the apoptotic signal into cells, and the antibody CH-11 works as an agonist.

After Fas ligand was cloned by Nagata's research group (reference 3), Fas antigen was begun to be called as Fas, and the ligand as Fas ligand.

References

1. Yonehara, S., Ishii, A. and Yonehara, M. (1989). A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor. J. Exp. Med. 169, 1747-1756.
2. Itoh, N., Yonehara, S., Ishii, A., Yonehara, M., Mizushima, S., Sameshima, M., Hase, A., Seto, Y. and Nagata, S. (1991). The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 66, 233-243.
3. Suda, T., Takahashi, T., Golstein, P. and Nagata, S. (1993). Molecular cloning and expression of the Fas ligand: a novel member of the tumor necrosis factor family. Cell 75, 1169-1178.

===========================================
Shin Yonehara, Ph.D.
Institute for Virus Research
Kyoto University
Kawahara-cho, Shogoin, Sakyo, Kyoto 606-01
Japan

TEL: 81-75-751-4783
FAX: 81-75-751-4784
E-mail: syonehar@virus.kyoto-u.ac.jp
============================================