In 1989 we published a paper describing the discovery of an apoptosis-inducing receptor [1]. We named this receptor APO-1, anticipating that it might be the first of a series of apoptosis-inducing receptors. Yonehara et al.[2] also described a cell surface molecule named Fas that could be triggered to induce cytotoxicity by an agonistic monoclonal antibody. Sequencing and cloning of the APO-1/Fas proteins and cDNAs, respectively, showed that APO-1 and Fas were identical [3, 4]. The 5th Workshop on Leukocyte Typing [5] suggested the name CD95 for the receptor. CD95 (APO-1/Fas) belongs to the subfamily of death receptors which is part of the TNF-receptor (TNF-R) superfamily. Members of this family are characterized by two to five copies of cysteine-rich extracellular repeats. Death receptors have an intracellular death domain (DD). The DD is essential for transduction of the apoptotic signal.

CD95 is a widely expressed glycosylated cell surface molecule of approximately 45 to 52 kDa (335 amino acids). It is a type I transmembrane receptor and can also occur in several soluble forms [3, 4, 6]. Soluble CD95 is generated by differential splicing with the transmembrane part spliced out. The human CD95 gene, APT, was localized to chromosome 10q23 and the mouse gene to chromosome 19 [7, 8]. Expression of the CD95 gene and cell surface protein are enhanced by IFN-and TNF and by activation of lymphocytes [9–11]. Under physiological conditions CD95-mediated apoptosis is triggered by the natural ligand (L) of the receptor, CD95L. CD95L is expressed in a more restricted way than CD95. CD95L was cloned from the cDNA of a killer cell (PC60-d10S) and shown to be a TNF-related type II transmembrane molecule [12]. The mouse and human CD95L genes were mapped to chromosome 1 [13, 14]. Killer cells expressing CD95L were shown to kill target cells in a Ca2+-independent fashion via CD95–CD95L interaction [15]. In addition,