Tumor necrosis factors (TNF) receptor (TNFR) family is consisting of a group of proteins with an extracellular domain rich in cysteine residues. These receptors are activated by specific TNF ligands. There are about 30 TNF receptors having been reported in humans.
Most TNF receptors form trimeric complexes in the plasma membrane as the active form and these receptors bind to TNF ligands as multimeric entities. Signaling through these receptors involves with cytoplasmic adaptor proteins (such as TRADD and TRAF1) as downstream. TNF receptors not only play a key role in apoptosis and inflammation but also involve in other signal transduction pathways, for example, survival, proliferation and differentiation. Some TNF receptors contain a ‘death domains’ which is crucial for the initiation of an apoptotic response.
TNFR1 is found ubiquitously throughout every cell in the body, while its counterpart TNFR2 is more restrictively expressed on certain immune subpopulations. Normally, TNFα signaling through TNFR1 pathway will lead to apoptosis through the caspase system. On the other hand TNFα signaling through TNFR2 will lead to cell survival through activation of NF-κB pathway. However, it has been found that autoreactive T Cells have a defective immuno-proteasome which causes the inability to activate the NF-κB pathway when stimulated through TNFR2.