Human 4-1BB receptor was expressed from CHO K1 cells. The protein was purified by affinity and size exclusion chromatography. The protein carries human IgG1 Fc tag at the C-terminus. The human IgG1 Fc tag can be digested by Factor X leaving the 4-1BB protein sequence with digestion site at the C-terminus. 4-1BB is a member of TNFR superfamily. Along with its ligand (4-1BBL, Tumor necrosis factor ligand superfamily member 9), the complex exhibits architecture common for other TNF receptor-ligand complexes, i.e. three units of 4-1BB bind to one trimeric unit of 4-1BBL (1). 4-1BB is not expressed on naïve T-cells, however it is rapidly upregulated after TCR stimulation by MHC/peptide complex as well as stimulation by Interleukin-2 and Interleukin-4 (2). As a result of binding, cytoplasmic tails of the receptor interact with TRAF1, TRAF2 and TRAF3, through which the interaction is able to costimulate activation of resting T-cells independently of CD28 (3, 4). Therefore, stimulation of 4-1BB may be important component of certain anti-tumor therapies.

1. Chin, S. Michael, et al. “Structure of the 4-1BB/4-1BBL complex and distinct binding and functional properties of utomilumab and urelumab.” Nature communications 9.1 (2018): 1-13.
2. Pollok, Karen E., Seung H. Kim, and Byoung S. Kwon. “Regulation of 4‐1BB expression by cell‐cell interactions and the cytokines, interleukin‐2 and interleukin‐” European journal of immunology 25.2 (1995): 488-494.
3. Saoulli, Katina, et al. “CD28-independent, TRAF2-dependent costimulation of resting T cells by 4-1BB ligand.” The Journal of experimental medicine 187.11 (1998): 1849-1862.
4. Jang, Ihn K., et al. “Human 4-1BB (CD137) signals are mediated by TRAF2 and activate nuclear factor-κB.” Biochemical and biophysical research communications 242.3 (1998): 613-620.