Tumor Necrosis Factor Receptor-I (TNF RI, also known as p55/p60) and TNF RII (also known as p75/p80) are both high affinity receptors for TNF-alpha and -beta, potent mediators of multiple aspects of inflammatory immune responses. Both RI and RII are prototypic members of the TNF receptor superfamily and have been designated TNFRSF1A and TNFRSF1B, respectively. Whereas all cell types are thought to express TNF RI, TNF RII expression is limited primarily to hematopoietic cells and cells of the immune system. Most of the biological functions of TNF are mediated via TNF RI. Soluble forms of both TNF RI and TNF RII, generated as a result of proteolytic cleavage of the extracellular domains, have been detected in vivo in various biological fluids. The soluble TNF receptors can bind TNF with high affinity and functions as TNF antagonists.
TNF receptors are thought to form homotrimers or oligomers upon ligand binding. The monomers of both TNF receptors subtypes have similar extracellular domains including four cysteine-rich repeats characteristic of the TNF receptor superfamily. However, the intracellular domains differ, and consequently, the receptors exhibit different signaling capabilities. For instance, although both are capable of interacting with adaptor proteins upstream of NF-kB activation, only TNF RI has a cytoplasmic ""death domain"" upstream of caspase-dependent apoptosis cascades. Soluble forms of both TNF receptors can be generated via proteolytic cleavage.