4-1BB receptor

4-1BB (or human 4-1BBL receptor) is an inducible T cell surface protein belonging to the TNF receptor superfamily. It is alternatively known as TNFR-SF9, CD137, and ILA. The 255 amino acid is a type I transmembrane protein having in its extracellular domain four of the cysteine-rich motifs that are characteristic of the TNF receptor superfamily. The 30 kDa glycoprotein exists both as a monomer and as a dimer on T cells. The human and mouse proteins share 60% amino acid identity. 4-1BB is absent from naive T cells, but it is upregulated and continually expressed following T cell activation. The natural ligand, 4-1BBL, is a member of the TNF superfamily and is expressed on activated antigen presenting cells including dendritic cells, macrophages, and B cells. Crosslinking of 4-1BB by 4-1BBL or by agonistic antibodies transmits a potent co stimulatory signal that enhances the effect of other activating signals such as PHA or antiCD3 antibodies. 4-1BB signals through the TFAF2NIK pathway resulting in activation of NFκB and ultimately promoting proliferation and survival of T cells.