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The molecular basis of X-linked severe combined immunodeficiency: defective cytokine receptor signaling.

X-linked severe combined immunodeficiency (XSCID) is an inherited disease characterized by profoundly diminished cell-mediated and humoral immunity. XSCID was found to result from mutations in the interleukin-2 (IL-2) receptor gamma chain. Knowledge of the genetic defect has important implications for prenatal and postnatal diagnosis, carrier female identification, and the possibility of gene therapy. The fact that the phenotype and clinical manifestations in XSCID are more severe than the abnormalities found in humans or mice deficient in IL-2 led to the speculation and subsequent confirmation that the IL-2 receptor is not the only receptor to contain the gamma chain. Instead, the gamma chain is also a component of the receptors for IL-4, IL-7, IL-9, and IL-15 and is now denoted as the common cytokine receptor gamma chain, gamma c. The role of gamma c in signaling and lymphoid development and the implications of a shared receptor component are discussed.