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.
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.
He
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YW
Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33136.
Adkins
B
B
Furse
R K
RK
Malek
T R
TR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D002460:Cell Line; D000939:Epitopes / Q000276:immunology; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D051381:Rats; D011917:Rats, Inbred Lew; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000502:physiology; D019948:Receptors, Interleukin-4; D020395:Receptors, Interleukin-7; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007376:Interleukin-2; D015851:Interleukin-7; D018123:Receptors, Interleukin; D015375:Receptors, Interleukin-2; D019948:Receptors, Interleukin-4; D020395:Receptors, Interleukin-7; D015847:Interleukin-4