• Purity

  >95%, by SDS-PAGE under reducing conditions and visualized by silver stain

• Endotoxin Level

  <0.01 EU per 1 μg of the protein by the LAL method.  

• Activity

  Measured by its binding ability in a functional ELISA. When Recombinant Rat 4‑1BB/TNFRSF9/CD137 Fc Chimera is present at 100 ng/mL, the concentration of Recombinant Mouse 4‑1BB Ligand/TNFSF9 (Catalog # ) that produces 50% of the optimal binding response is approximately 5‑25 ng/mL.

• Source

  Mouse myeloma cell line, NS0-derived

  Rat 4-1BB (Thr24-Val188) Accession # NP_001020944	IEGRMDP	Mouse IgG2A (Glu98-Lys330)
  N-terminus		C-terminus

• Accession #

• N-terminal Sequence    
  Analysis

  Thr24

• Structure / Form

  Disulfide-linked homodimer

• Predicted Molecular Mass

  44.9 kDa (monomer)

• SDS-PAGE

  60-65 kDa, reducing conditions

Background: 4-1BB/TNFRSF9/CD137

4‑1BB, also known as CD137 and TNFRSF9, is an approximately 30 kDa transmembrane glycoprotein in the TNF receptor superfamily. 4‑1BB functions in the development and activation of multiple immune cells (1). Mature rat consists of a 166 amino acid (aa) extracellular domain (ECD) with four TNFR cysteine‑rich repeats, a 21 aa transmembrane segment, and a 48 aa cytoplasmic domain. Within the ECD, rat 4‑1BB shares 60% and 79% aa sequence identity with human and mouse 4‑1BB, respectively. 4‑1BB is expressed as a disulfide‑linked homodimer on various populations of activated T cells including CD4  ⁺, CD8  ⁺, memory CD8  ⁺, NKT, and regulatory T cells (2‑5) as well as on myeloid and mast cell progenitors, dendritic cells, mast cells, and bacterially infected osteoblasts (6‑9). It binds with high affinity to the transmembrane 4‑1BB Ligand/TNFSF9 which is expressed on antigen presenting cells and myeloid progenitor cells (6, 10). This interaction co‑stimulates the proliferation, activation, and/or survival of the 4‑1BB expressing cell (2‑5, 10). It can also enhance the activation‑induced cell death of repetitively stimulated T cells (10). Mice lacking 4‑1BB show augmented T cell activation, perhaps due to its absence on regulatory T cells (11). 4‑1BB can associate with OX40 on activated T cells, forming a complex that responds to either ligand and inhibits Treg and CD8  ⁺ T cell proliferation (12). Reverse signaling through 4‑1BB Ligand inhibits the development of dendritic cells, B cells, and osteoclasts (6, 9) but supports mature dendritic cell survival and co‑stimulates the proliferation and activation of mast cells (7, 8). 4‑1BB activation enhances CD8  ⁺ T cell and NK cell mediated anti‑tumor immunity (13). It also contributes to the development of inflammation in high fat diet‑induced metabolic syndrome (14). Soluble forms of 4‑1BB and 4‑1BB Ligand circulate at elevated levels in the serum of rheumatoid arthritis and hematologic cancer patients, respectively (15, 16).

• References:

1. Wang, C. et al. (2009) Immunol. Rev. 229:192.

2. Wen, T. et al. (2002) J. Immunol. 168:4897.

3. Pulle, G. et al. (2006) J. Immunol. 176:2739.

4. Zheng, G. et al. (2004) J. Immunol. 173:2428.

5. Kim, D. et al. (2008) J. Immunol. 180:2062.

6. Lee, S. et al. (2008) Nat. Immunol. 9:917.

7. Choi, B.K. et al. (2009) J. Immunol. 182:4107.

8. Nishimoto, H. et al. (2005) Blood 106:4241.

9. Saito, K. et al. (2004) J. Biol. Chem. 279:13555.

10. Alderson, M.R. et al. (1994) Eur. J. Immunol. 24:2219.

11. Lee, S. et al. (2005) J. Immunol. 174:6803.

12. Ma, B.Y. et al. (2005) Blood 106:2002.

13. Choi, B.K. et al. (2010) J. Immunol. 185:1404.

14. Kim, C. et al. (2011) Diabetes 60:3159.

15. Michel, J. et al. (1998) Eur. J. Immunol. 28:290.

16. Salih, H.R. et al. (2001) J. Immunol. 167:4059.

• Entrez Gene IDs:

  3604 (Human); 21942 (Mouse); 500590 (Rat); 102127961 (Cynomolgus Monkey)

• Alternate Names:

  4-1BB ligand receptor; 41BB; 4-1BB; CD137 antigen; CD137; CD137MGC2172; CDw137; FLJ43501; ILA; ILAhomolog of mouse 4-1BB; induced by lymphocyte activation (ILA); interleukin-activated receptor, homolog of mouse Ly63; receptor protein 4-1BB; T cell antigen ILA; T-cell antigen 4-1BB homolog; T-cell antigen ILA; TNFRSF9; tumor necrosis factor receptor superfamily member 9; tumor necrosis factor receptor superfamily, member 9