• Purity

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

• Endotoxin Level

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

• Activity

  Measured by its ability to block 4-1BBL-induced IL-2 secretion by mouse T cells. The ED    ₅₀ for this effect is 0.3-1 µg/mL in the presence of 0.4 µg/mL of recombinant mouse 4-1BBL. Measured by its ability to bind recombinant mouse 4-1BB Ligand in a functional ELISA.

• Source

  Mouse myeloma cell line, NS0-derived

  Mouse 4-1BB (Val24-Leu187) Accession # P20334	DIEGRMD	Human IgG1 (Pro100-Lys330)
  N-terminus		C-terminus

• Accession #

• N-terminal Sequence    
  Analysis

  Val24

• Structure / Form

  Disulfide-linked homodimer

• Predicted Molecular Mass

  44.3 kDa (monomer)

• SDS-PAGE

  62-66 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 mouse 4-1BB consists of a 164 amino acid (aa) extracellular domain (ECD) with four TNFR cysteine‑rich repeats, a 21 aa transmembrane segment, and a 48 aa cytoplasmic domain (2). Within the ECD, mouse 4-1BB shares 60% and 79% aa sequence identity with human and rat 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 (3-6) as well as on myeloid and mast cell progenitors, dendritic cells, mast cells, and bacterially infected osteoblasts (7-10). It binds with high affinity to the transmembrane 4-1BB Ligand/TNFSF9 which is expressed on antigen presenting cells and myeloid progenitor cells (7, 11). This interaction co‑stimulates the proliferation, activation, and/or survival of the 4-1BB expressing cell (3-6, 11). It can also enhance the activation-induced cell death of repetitively stimulated T cells (11). Mice lacking 4-1BB show augmented T cell activation, perhaps due to its absence on regulatory T cells (12). 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 (13). Reverse signaling through 4-1BB Ligand inhibits the development of dendritic cells, B cells, and osteoclasts (7, 10) but supports mature dendritic cell survival and co‑stimulates the proliferation and activation of mast cells (8, 9). 4‑1BB activation enhances CD8  ⁺ T cell and NK cell mediated anti-tumor immunity (14). It also contributes to the development of inflammation in high fat diet-induced metabolic syndrome (15). Soluble forms of 4-1BB and 4-1BB Ligand circulate at elevated levels in the serum of rheumatoid arthritis and hematologic cancer patients, respectively (16, 17).

• References:

1. Kwon, B.S. and S.M. Weissman (1989) Proc. Natl. Acad. Sci. USA 86:1963.

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