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Sharing of a Common γ Chain, γc, by the IL-2, IL-4, and IL-7 Receptors: Implications for X-Linked Severe Combined Immunodeficiency (XSCID)

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Mechanisms of Lymphocyte Activation and Immune Regulation V

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 365))

Summary

X-linked severe combined immunodeficiency (XSCID) is a disease characterized by profoundly diminished cellular and humoral immunity1,2. XSCID is by far the most common form of SCID, accounting for at least half of all cases. It is characterized by the presence of few or no T cells; B cells are present at relatively normal levels but are nonfunctional. In this manuscript, we will first summarize the studies that led to the discovery that the molecular basis for XSCID is mutation of the IL-2 receptor γ chain (IL-2Rγ)3. Because defects in humans with XSCID are greater than those found in IL-2 deficient mice or humans, we speculated that the IL-2Rγ was likely to be a component of more than one cytokine receptor3. This led to the discovery that IL-2Rγ is in fact a common γ chain, γc, which is also a component of both the IL-44,5 and IL-76 receptors. Given the importance of IL-2, IL-4, and IL-7 in B-cell and T-cell function, this finding helps to explain the basis for the immunological defects found in XSCID patients. Moreover, it provides important insights into understanding the molecular basis as to how these cytokines can exhibit both overlapping and competing activities.

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Authors and Affiliations

  1. Section on Pulmonary and Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Warren J. Leonard, Masayuki Noguchi & Sarah M. Russell

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  1. Warren J. Leonard
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  2. Masayuki Noguchi
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  3. Sarah M. Russell
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Editors and Affiliations

  1. Department of Medicine, University of California, Irvine, CA, 92717-4069, USA

    Sudhir Gupta

  2. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892-0001, USA

    William E. Paul

  3. Department of Microbiology and Immunology, University of California, San Francisco, CA, 94143-0552, USA

    Anthony DeFranco

  4. Department of Immunology, University of Washington, Seattle, WA, 98915, USA

    Roger M. Perlmutter

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Leonard, W.J., Noguchi, M., Russell, S.M. (1994). Sharing of a Common γ Chain, γc, by the IL-2, IL-4, and IL-7 Receptors: Implications for X-Linked Severe Combined Immunodeficiency (XSCID). In: Gupta, S., Paul, W.E., DeFranco, A., Perlmutter, R.M. (eds) Mechanisms of Lymphocyte Activation and Immune Regulation V. Advances in Experimental Medicine and Biology, vol 365. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0987-9_23

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  • DOI: https://doi.org/10.1007/978-1-4899-0987-9_23

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