The interferon gamma receptor.

Abstract

Interferon-gamma (IFN gamma) can regulate in vitro and in vivo a number of functions on a variety of cell types including some with no known immune functions. Recent work has indicated that IFN gamma exerts its effects upon interaction with a specific receptor on the cell surface. An IFN gamma receptor has been detected in a large variety of cell types of human and murine origins. Species specificity of IFN gamma appears to be a function of ligand-receptor interaction. In the human system, the IFN gamma receptor is a protein of 90 kd molecular weight. IFN gamma is internalized and degraded at a constant rate. The continuous uptake of IFN gamma is due to the presence of an intracellular receptor pool and to a mechanism of receptor recycling. By comparing the relationship between receptor occupancy and biologic response induction in macrophages, two activation mechanisms became apparent. Induction of certain functions such as H2O2 secretion, expression of Fc receptor or IA appeared to require only a single round of receptor occupancy. However, induction of more complex functions such as non-specific tumoricidal activity appeared to require three to four rounds of receptor occupancy. These results thus support the concept that IFN gamma induces different activities by triggering a different pathway at the cell surface and/or inside of the cell.