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)
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.
KeywordsCytokine Receptor Severe Combine Immunodeficiency Primary Immunodeficiency Disease Immunological Defect Cytokine Receptor Superfamily
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