TNF receptors--how they function and interact.

Tumor necrosis factor (TNF) is a pleiotropic cytokine regulating various immune and inflammatory reactions. It induces cellular responses upon binding to specific cell surface receptors of two distinct molecular species--p55 and p75 TNF receptors (TNF-Rs). Cloning of the respective cDNAs and obtaining the receptor-specific molecular tools such a agonistic and blocking monoclonal antibodies, TNF muteins with exclusive ability to bind to only one receptor type, as well as generation of TNF-R mutants by site-directed mutagenesis enabled researchers to answer key questions of the biology of initial steps in the cascade of TNF signal transduction. The presented mini-review describes the mode of function of the two receptors and discusses the possible ways of interaction between them.