Expression and function of the gamma c subunit of the IL-2, IL-4, and IL-7 receptors. Distinct interaction of gamma c in the IL-4 receptor.

Abstract

IL-2R, IL-4R, and IL-7R share a common subunit referred to as gamma c and the IL-13R has been proposed to contain gamma c as a subunit. In this report we have used two novel mAbs (3E12 and 4G3) to distinct epitopes of mouse gamma c to determine its lymphoid cell distribution and to examine whether gamma c uses similar epitopes to interact with different cytokines and cytokine receptors. FACS analysis revealed that gamma c is expressed in most lymphocytes, myeloid cells, embryonic thymocytes, and lymphoid cell lines. Results from radiolabeled ligand binding studies, biochemical analysis of ligand-receptor cross-linked complexes, and cytokine bioassays indicate that the epitope defined by mAb 4G3 closely defines the IL-7 binding region of gamma c and overlaps the IL-2 binding region of gamma c. These studies also indicate that gamma c interacts with IL-4 in the context of the IL-4R in a manner that is distinct from its role in the IL-2R and IL-7R and suggest that the 3E12 epitope defines a region of gamma c that intimately interacts with the IL-4R. The B9 plasmacytoma, which proliferates in response to IL-4 and IL-13, was shown to not express gamma c. Thus, at least in some circumstances, gamma c is dispensable for signaling via the IL-4R and is not a required subunit of the IL-13R.