The biology and biochemistry of interferon-gamma and its receptor.

Interferon-gamma (IFN gamma) is an important immunomodulatory cytokine produced by activated T cells and NK cells that plays a pivotal role in promoting host defense. IFN gamma is distinguished from IFN alpha and IFN beta by its ability to regulate a number of immune functions. IFN gamma induces its biologic effects by interacting with a specific IFN gamma receptor expressed at the cell surface. Recently, IFN gamma receptors have been purified from human and murine cells and their cDNAs cloned and expressed. This work has revealed that IFN gamma receptors are 90 kDa, single chain glycoproteins that bind ligand with high affinity in a species specific manner. There appears to be only a single type of IFN gamma receptor that is expressed on nearly all cell types. Whereas this single polypeptide is sufficient to confer ligand binding and processing activity to transfected cells, a second, as yet undefined, component is required to form a functionally active IFN gamma receptor. The identity of this second component is currently being investigated. In addition, recent work has revealed novel structure-function relationships that exist within the IFN gamma receptor's intracellular domain. This work has shown that distinct portions of the intracellular domain are differentially responsible for mediating different biologic activities of the receptor.