GITR (glucocorticoid-induced tumor necrosis factor receptor, also named AITR, activation-inducible TNF R family member), is a 228 amino acid (aa) type I transmembrane protein belonging to the TNF R family and has been designated TNFRSF18. The GITR cytoplasmic domain has striking homology with the cytoplasmic domain of 4-1BB and CD27. Human GITR shares 55% homology with murine GITR. GITR 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 stimulation or by treatment with anti-CD3 plus anti-CD28, or PMA plus ionomycin. Human GITR ligand was identified from human umbilical vein endothelial cells and is a 177 aa polypeptide belonging to the TNF superfamily (TNFSF18). Ligation of GITR can activate NF-kappa B through TRAF2, and protect T cells from TCR activation-induced cell death. It has been proposed that GITR ligand and GITR may modulate T lymphocyte functions.
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