• Purity

  >95%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie? Blue Staining.

• Endotoxin Level

  <0.10 EU per 1 μg of the protein by the LAL method.  

• Activity

  Measured by its binding ability in a functional ELISA. When Recombinant Cynomolgus Monkey GITR/TNFRSF18 Fc Chimera is immobilized at 0.5 μg/mL, 100 μL/well, the concentration of biotinylated recombinant human GITR Ligand/TNFSF18 that produces 50% of the optimal binding response is 8-40 ng/mL.

• Source

  Chinese Hamster Ovary cell line, CHO-derived

  Cynomolgus Monkey GITR/TNFRSF18 (Gln20-Glu155) Accession # XP_005545180	IEGRMD	Human IgG1 (Pro100-Lys330)
  N-terminus		C-terminus

• Accession #

• N-terminal Sequence    
  Analysis

  No results obtained. Gln20 inferred from enzymatic pyroglutamate treatment revealing Arg21

• Structure / Form

  Disulfide-linked homodimer

• Predicted Molecular Mass

  41 kDa

• SDS-PAGE

  49-60 kDa, reducing conditions

Data Images

Background: GITR/TNFRSF18

GITR (glucocorticoid-induced tumor necrosis factor receptor), also known as AITR and TNFRSF18, is a 40 kDa transmembrane glycoprotein that functions in immune regulation (1, 2). Mature human GITR consists of a 137 amino acid (aa) extracellular domain (ECD) with three tandem TNF R cysteine-rich repeats, a 21 aa transmembrane segment, and a 58 aa cytoplasmic domain (3, 4). Within the ECD region, cyno GITR shares 89.8% and 53.2% aa sequence identity with human and mouse GITR, respectively. Alternative splicing generates an isoform with a short deletion in the cytoplasmic domain and a potentially secreted isoform that is substituted within the third TNF R repeat and lacks the transmembrane and cytoplasmic regions. GITR is expressed on CD4  ⁺CD25  ⁺ regulatory T cells (Treg) as well as on subsets of thymocytes, lymph node cells, and splenocytes (4-6), and it is up-regulated on antigen-activated conventional CD4  ⁺ and CD8  ⁺ T cells (3, 4, 6, 7). GITR binding by GITR Ligand/TNFSF18 co-stimulates the proliferation and activation of CD4  ⁺ or CD8  ⁺ conventional T cells (3, 7-9). It also induces the proliferation of Treg (8, 10) but inhibits the ability of Treg to suppress immune responses (5, 8, 11-13). This can result in the development of autoimmunity, increased tumor cell killing by effector T cells (5, 11), and increased inflammation in arthritis, allergic asthma, and inflammatory bowel disease (10, 14). GITR is also expressed on sympathetic neurons where it enhances NGF-induced neurite outgrowth and branching (15).

• References:

1. Clouthier, D.L. and T.H. Watts (2014) Cytokine Growth Factor Rev. 25:91.

2. Ronchetti, S. et al. (2015) J. Immunol. Res. 2015:171520.

3. Gurney, A.L. et al. (1999) Curr. Biol. 9:215.

4. Kwon, B. et al. (1999) J. Biol. Chem. 274:6056.

5. Shimizu, J. et al. (2002) Nat. Immunol. 3:135.

6. Nocentini, G. et al. (1997) Proc. Natl. Acad. Sci. USA 94:6216.

7. Muriglan, S.J. et al. (2004) J. Exp. Med. 200:149.

8. Ronchetti, S. et al. (2004) Eur. J. Immunol. 34:613.

9. Tone, M. et al. (2003) Proc. Natl. Acad. Sci. USA 100:15059.

10. Ephrem, A. et al. (2013) Eur. J. Immunol. 43:2421.

11. Ko, K. et al. (2005) J. Exp. Med. 202:885.

12. Ji, H. et al. (2004) J. Immunol. 172:5823.

13. Stephens, G.L. et al. (2004) J. Immunol. 173:5008.

14. Patel, M. et al. (2005) Eur. J. Immunol. 35:3581.

15. O'Keeffe, G.W. et al. (2008) Nat. Neurosci. 11:135.

• Long Name:

  Glucocorticoid Induced TNF Receptor Family Related Gene

• Entrez Gene IDs:

  8784 (Human); 21936 (Mouse); 500598 (Rat); 102146362 (Cynomolgus Monkey)

• Alternate Names:

  Activation-inducible TNFR family receptor; AITR; AITRTNF receptor superfamily activation-inducible protein; CD357 antigen; CD357; GITR; GITR-D; GITRtumor necrosis factor receptor superfamily member 18; Glucocorticoid-induced TNFR-related protein; TNFRSF18; tumor necrosis factor receptor superfamily, member 18