4-1BB/CD137 Extracellular Domain (human, recombinant)

4-1BB, also known as CD137, is a type I transmembrane glycoprotein and member of the TNF receptor superfamily with roles in T cell-mediated immunity.¹ It is composed of an N-terminal extracellular domain comprised of a signaling sequence and four cysteine-rich pseudo repeats (CRDs), a helical transmembrane domain, and a cytoplasmic signaling domain.² 4-1BB is transiently expressed on antigen-primed activated T cells, activated natural killer (NK) cells, and mature dendritic cells. Binding of homotrimeric 4-1BB ligand on antigen-primed T cells induces NF-κB and MAPK signaling through TNF receptor-associated factors (TRAFs) and, when the T cell is co-stimulated by other factors, induces PI3K signaling.^3,1 This bidirectional signaling event promotes clonal expansion, differentiation, and survival of T cells, as well as polarizes T helper cells.⁴ Knockout of Tnfrsf9, the gene encoding 4-1BB, reduces pancreatic islet accumulation of β-cell-autoreactive CD8⁺ T cells in a mouse model of type 1 diabetes mellitus. Administration of an anti-4-1BB antibody prolongs survival and reverses renal damage, production of autoantibodies, and immune complex deposition in lupus-prone NZB X NZW F₁ mice. Cayman’s 4-1BB/CD137 Extracellular Domain (human, recombinant) protein can be used for ELISA. This protein is a disulfide-linked homodimer. The reduced monomer, comprised of 4-1BB (amino acids 25-186) fused to His-tagged human IgG1 Fc at its C-terminus, consists of 409 amino acids, has a calculated molecular weight of 45.2 kDa, and a predicted N-terminus of Gln25 after signal peptide cleavage. As a result of glycosylation, the monomer migrates at approximately 60 to 65 kDa by SDS-PAGE under reducing conditions.

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1. So, T., and Ishii, N. The TNF–TNFR family of co-signal molecules. Co-signal molecules in T cell activation 53-84 (2019).

2. Chin, S.M., Kimberlin, C.R., Roe-Zurz, Z., et al. Structure of the 4-1BB/4-1BBL complex and distinct binding and functional properties of utomilumab and urelumab. Nat. Commun. 9(1), 4679 (2018).

3. Barsoumian, H.B., Batra, L., Shrestha, P., et al. A novel form of 4-1BBL prevents cancer development via nonspecific activation of CD4⁺ T and natural killer cells. Cancer Res. 79(4), 783-794 (2019).

4. Wong, H.Y., and Schwarz, H. CD137 / CD137 ligand signalling regulates the immune balance: A potential target for novel immunotherapy of autoimmune diseases. J. Autoimmun. 112, 102499 (2020).