Human GITR Ligand/TNFSF18 Antibody

GITR (glucocorticoid-induced TNF receptor superfamily-related protein, also named AITR, activation-inducible TNF receptor superfamily-related protein) and GITR Ligand (GITRL) are novel members of the TNF receptor (TNFR) and TNF superfamilies (SF) that have been designated TNFRSF18 and TNFSF18, respectively. Human GITR Ligand cDNA encodes a 177 amino acid type II membrane protein. The carboxy-terminal extracellular domain shows sequence identity to TNF/TNFSF2 (21%), Fas ligand/TNFSF6 (21%), TRAIL/TNFSF10 (18%), and lymphotoxin alpha /TNFSF1 (18%). GITR Ligand is constitutively expressed in human umbilical vein endothelial cells but is not expressed in resting or stimulated T cell lines, B cell lines or peripheral blood mononuclear cells. GITR, the receptor for GITR Ligand, is expressed at low levels in peripheral blood T cells, bone marrow, thymus, spleen and lymph nodes. In contrast to mouse GITR, expression of human GITR is not induced by treatment with dexamethasone, but is up-regulated by antigen-receptor stimulation or by treatment with soluble anti-CD3 plus anti-CD28 or PMA plus ionomycin. Ligation of GITR has been found to induce nuclear factor (NF)-kappa B activation via TNF receptor-associated factor 2 and protect cells from TCR activation-induced cell death. It has been proposed that GITR Ligand and GITR may modulate T lymphocyte functions in peripheral tissues.