The IL-2R γ-chain is an indispensable subunit for the functional IL-2R. Recently, mutations of the γ-chain have been reported to be closely associated with X-linked severe combined immunodeficiency (XSCID). The present study reveals that three patients with XSCID have three different mutations in the γ-chain; a point mutation, a two consecutive-base deletion, and lack of the second exon in mRNA. The point mutation that we have detected is C to T, which results in one amino acid substitution of valine for alanine in the extracellular domain of the IL-2R γ-chain (named AV mutant). The two- base deletion detected causes a frame shift of the coding region in the SH2 subdomain in the cytoplasmic domain (named tSH mutant). Transfection studies performed with the mutant γ-chains demonstrated that the AV mutant and tSH mutant failed to bind to IL-2 and to transduce growth signals, respectively. These findings indicate that the γ-chain gene mutations that accompany XSCID induce loss on the γ-chain function, possibly resulting in stagnation of the differentiation and development of T cells.
|Number of pages||8|
|Journal||Journal of Immunology|
|Publication status||Published - 1994 Aug 1|
ASJC Scopus subject areas
- Immunology and Allergy