Human GITR Ligand/TNFSF18 Fluorescein-conjugated 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 GITRL cDNA encodes a 177 amino acid residues 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%). GITRL 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 GITRL, 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 GITRL and GITR may modulate T lymphocyte functions in peripheral tissues.