Abstract
Mutations in γc, a shared receptor subunit for interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21, lead to profound impairment in T-cell and natural killer (NK) cell development and are responsible for X-linked severe combined immunodeficiency disease (X-SCID). Considerable attention has been paid to how the lack of γc expression and signaling results in failed lymphocyte development. However, γc is also an essential ligand binding subunit for γc-dependent cytokine receptors. Molecular modeling in conjunction with site-directed mutagenesis of γc indicates that a common mechanism is responsible for the ability of γc to bind multiple cytokines. This notion is related to instances in which mutations in the extracytoplasmic region of γc resulted in X-SCID.