Recombinant Mouse Fas Ligand/TNFSF6 Protein

Fas Ligand (FasL), also known as CD178, CD95L, or TNFSF6, is a 40 kDa type II transmembrane member of the TNF superfamily of proteins. Its ability to induce apoptosis in target cells plays an important role in the development, homeostasis, and function of the immune system (1). Mature mouse Fas Ligand consists of a 179 amino acid (aa) extracellular domain (ECD), a 22 aa transmembrane segment, and a 78 aa cytoplasmic domain (2). Within the ECD, mouse Fas Ligand shares 81% and 93% aa sequence identity with human and rat Fas Ligand, respectively. Alternate splicing generates a 16 kDa isoform that corresponds to the C-terminal 69 amino acids of the ECD (3). Both mouse and human Fas Ligand are active on mouse and human cells (4, 5). Fas Ligand is expressed as a nondisulfide-linked homotrimer on activated CD4⁺ Th1 cells, CD8⁺ cytotoxic T cells, and NK cells (1). Fas Ligand binding to Fas/CD95 on an adjacent cell triggers apoptosis in the Fas‑expressing cell (2, 4). Fas Ligand also binds DcR3 which is a soluble decoy receptor that interferes with Fas Ligand-induced apoptosis (6). Fas Ligand can be released from the cell surface by metalloproteinases as a 26 kDa soluble molecule which remains trimeric (7, 8). Shed Fas Ligand retains the ability to bind Fas, although its ability to trigger apoptosis is dramatically reduced (7, 8). In the absence of TGF‑ beta, however, Fas Ligand/Fas interactions instead promote neutrophil-mediated inflammatory responses (5, 9). Fas Ligand itself transmits reverse signals that costimulate the proliferation of freshly antigen-stimulated T cells (10). Fas Ligand‑induced apoptosis plays a central role in the development of immune tolerance and the maintance of immune privileged sites (11). This function is exploited by tumor cells which evade immune surveillance by upregulating Fas Ligand to kill tumor infiltrating lymphocytes (9, 12). In gld mice, a Fas Ligand point mutation is the cause of severe lymphoproliferation and systemic autoimmunity (13, 14).