Molecular cloning and characterization of cynomolgus monkey Fas

The Fas-FasL system plays a crucial role in the maintenance of homeostasis in the immune system. To characterize the Fas/FasL system in macaque monkey s that are commonly used as experimental primates, we cloned and sequenced Fas cDNA derived from the cynomolgus monkey. The predicted amino acid seque nce consists of 331 amino acids with a calculated molecular weight of 35,80 0. The extracellular cysteine-rich motif of cynomolgus Fas is highly homolo gous to that of humans (96%), whereas the intracellular death domain has a relatively low similarity to that of humans (86%). An agonistic Fas antibod y (CH11) or cynomolgus Fast induced apoptosis in human Fas-transfected K562 cells in the presence of CHX but nor in the cynomolgus Fas transfectant. C H11 and Fast failed to trigger apoptosis in the transfectant expressing hum an-cynomolgus chimera Fas consisting mostly of human-derived extracellular region and cynomolgus-derived intracellular portion. On the other hand, the transfectant expressing cynomolgus-human chimera Fas with human-derived in tracellular region underwent apoptosis upon exposure to Fast. In addition, the virus-transformed, Fas-positive cynomolgus monkey cell line was highly sensitive to Fast. These findings suggest that the lack of apoptotic activi ty in the cynomolgus Fas transfectant in the human cell line might be relat ed to the species-specific structure of Fas, especially of the death domain . Human Immunology 61, 474-485 (2000). (C) American Society for Histocompat ibility and Immunogenetics, 2000. Published by Elsevier Science Inc.