Tumor necrosis factor ligand superfamily member 18
GITRL
Alternative names AITRL, TL6
Known ligands GITR
Origin Homo sapiens
Accession number Q9UNG2
Catalog number Protein construct Tag Expression host Biologically active Application
R1-030-1 GITRL ECD (50-177) His-tag, Fc-tag CHO Yes ELISA, WB, functional studies
R1-030-1a GITRL ECD (50-177) His-tag CHO Yes ELISA, WB, functional studies
R1-030-2 GITRL ECD (50-177) His-tag E. coli Yes ELISA, WB, functional studies, NMR, X-Ray
R1-030-3 GITR/GITRL complex Tag free CHO N/A NMR, X-Ray
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Human GITRL receptor was expressed from hamster CHO K1 cells. The protein was purified by affinity and size exclusion chromatography. The protein carries a hexa-histidine tag, as well as human IgG1 Fc tag at the C-terminus. The human IgG1 Fc tag can be digested by Factor X leaving the GITRL protein sequence with His-tag and digestion site at the C-terminus. Human GITRL assemblies into homotrimeric complex, with equilibrium between monomer and trimer (with trimer displaying higher binding affinity to GITR), which was not reported for other TNF family members (1). Binding of GITRL to GITR (Tumor necrosis factor receptor superfamily member 18) leads to abrogation of suppressive activity of Treg (CD4+CD25+) cells (2, 3), as well as stimulation of effector T-cells proliferation (4). In case of GITR/GITRL pathway, not only GITR but also GITRL signals inside the cells, which results incl.  macrophages producing pro-inflammatory factors (5, 6). GITRL is abundantly expressed in cerebral cortex, small intestine, ovary, testis, kidney and endothelial cells (7).

 

  1. Chattopadhyay, Kausik, et al. “Assembly and structural properties of glucocorticoid-induced TNF receptor ligand: Implications for function.” Proceedings of the National Academy of Sciences 104.49 (2007): 19452-19457.
  2. Shimizu, Jun, et al. “Stimulation of CD25+ CD4+ regulatory T cells through GITR breaks immunological self-tolerance.” Nature immunology 3.2 (2002): 135-142.
  3. McHugh, Rebecca S., et al. “CD4+ CD25+ immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor.” Immunity 16.2 (2002): 311-323.
  4. Ronchetti, Simona, et al. “Frontline: GITR, a member of the TNF receptor superfamily, is costimulatory to mouse T lymphocyte subpopulations.” European journal of immunology 34.3 (2004): 613-622.
  5. Shin, Hyun-Hee, et al. “Recombinant glucocorticoid induced tumor necrosis factor receptor (rGITR) induces NOS in murine macrophage.” FEBS letters 514.2-3 (2002): 275-280.
  6. Nocentini, Giuseppe, et al. “GITR/GITRL: more than an effector T cell co‐stimulatory system.” European journal of immunology 37.5 (2007): 1165-1169.
  7. Bastian, Frederic B., et al. “The Bgee suite: integrated curated expression atlas and comparative transcriptomics in animals.” Nucleic Acids Research 49.D1 (2021): D831-D847.