Recombinant Human GITR Ligand/TNFSF18 Protein

GITR Ligand, also known as TNFSF18 and TL6, is an approximately 30 kDa type II transmembrane glycoprotein in the TNF superfamily (1). Human GITR Ligand consists of a 50 amino acid (aa) cytoplasmic domain, a 21 aa transmembrane segment, and a 128 aa extracellular domain (ECD) (2, 3). Within the ECD, human GITR Ligand shares 56% and 60% aa sequence identity with mouse and rat GITR Ligand, respectively. GITR Ligand is expressed on antigen presenting cells, CD4^-CD8^- double negative thymic precursors, vascular endothelial cells, neurons, and in the eye (4‑11). Its expression is transiently up‑regulated by proinflammatory stimulation (4, 8, 11). The binding of GITR Ligand to GITR on mouse CD25⁺ Treg cells permits the reactivation of T cells from Treg-induced suppression, although this does not appear to occur in humans (5, 9, 12-14). GITR Ligand binding to GITR additionally provides a costimulatory signal to activated CD4⁺  and CD8⁺ T cells and NK cells (5, 6, 15, 16). This interaction also induces reverse signaling in GITR Ligand expressing dendritic cells to suppress cellular activation through the same pathway induced by the immunosuppressant dexamethasone (17). In the brain, GITR Ligand/GITR interactions enhance NGF-mediated neurite outgrowth from sympathetic neurons (10).