Impairment of ligand binding and growth signaling of mutant IL-2 receptor gamma-chains in patients with X-linked severe combined immunodeficiency

J Immunol. 1994 Aug 1;153(3):1310-7.

Abstract

The IL-2R gamma-chain is an indispensable subunit for the functional IL-2R. Recently, mutations of the gamma-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 gamma-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 gamma-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 gamma-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 gamma-chain gene mutations that accompany XSCID induce loss of the gamma-chain function, possibly resulting in stagnation of the differentiation and development of T cells.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Division
  • Cell Line
  • DNA Primers / chemistry
  • Gene Expression
  • Genes, fos
  • Genes, jun
  • Genes, myc
  • Humans
  • Ligands
  • Male
  • Molecular Sequence Data
  • Mutation
  • RNA, Messenger / genetics
  • Receptors, Interleukin-2 / physiology*
  • Severe Combined Immunodeficiency / immunology*
  • Signal Transduction

Substances

  • DNA Primers
  • Ligands
  • RNA, Messenger
  • Receptors, Interleukin-2