MOLECULAR-CLONING AND EXPRESSION OF THE FAS LIGAND, A NOVEL MEMBER OFTHE TUMOR-NECROSIS-FACTOR FAMILY

The Fas antigen (Fas) belongs to the tumor necrosis factor (TNF)/nerve growth factor receptor family, and it mediates apoptosis. Using a sol uble form of mouse Fas, prepared by fusion with human immunoglobulin F c, Fas ligand was detected on the cell surface of a cytotoxic T cell h ybridoma, PC60-d10S. A cell population that highly expresses Fas ligan d was sorted using a fluorescence-activated cell sorter, and its cDNA was isolated from the sorted cells by expression cloning. The amino ac id sequence indicated that Fas ligand is a type II transmembrane prote in that belongs to the TNF family. The recombinant Fas ligand expresse d in COS cells induced apoptosis in Fas-expressing target cells. North ern hybridization revealed that Fas ligand is expressed in activated s plenocytes and thymocytes, consistent with its involvement in T cell-m ediated cytotoxicity and in several nonlymphoid tissues, such as testi s.