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• W4313309973 endingPage "3483" @default.
• W4313309973 startingPage "3474" @default.
• W4313309973 abstract "Abstract The IL receptor common γ (γc) chain is required for the formation of high affinity cytokine receptor complexes for IL-2, IL-4, IL-7, IL-9, and IL-15, and for signals regulating cell survival, growth, and differentiation. Our current understanding of how γc chain associates with multiple ligands and receptor subunits is drawn largely from its structural homology to the human growth hormone (hGH) receptor and known structure of the hGH/hGH receptor complex. These receptors share distinct features in their extracellular portions and are believed to function by a mechanism of ligand-induced association of receptor subunits. Here, we report the first directed mutational analysis of the human γc chain by alanine scanning conducted across seven regions likely to contain residues required for intermolecular contact. Functionally distinct, neutralizing anti-γc mAbs were employed to define critical residues. One particular mAb, CP.B8, unique in its ability to inhibit IL-2-, IL-4-, IL-7-, and IL-15-induced proliferation and high affinity cytokine binding of normal T cells as an intact mAb and as a Fab fragment, localized critical residues to four noncontinuous stretches, namely residues in loops AB and EF of domain 1, in the interdomain segment, and in loop FG of domain 2. Notably, these residues form a contiguous patch on the γc chain surface in a three-dimensional structural model. These results provide functional evidence for the location of contact points on γc chain required for its association with multiple ligands." @default.
• W4313309973 created "2023-01-06" @default.
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• W4313309973 date "1998-10-01" @default.
• W4313309973 modified "2023-10-17" @default.
• W4313309973 title "Molecular Mapping with Functional Antibodies Localizes Critical Sites on the Human IL Receptor Common γ (γc) Chain" @default.
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• W4313309973 doi "https://doi.org/10.4049/jimmunol.161.7.3474" @default.
• W4313309973 hasPublicationYear "1998" @default.
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