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

Naoto Ishii, Hironobu Asao, Yutaka Kimura, Toshikazu Takeshita, Masataka Nakamura, Shigeru Tsuchiya, Tasuke Konno, Michiyuki Maeda, Takashi Uchiyama, Kazuo Sugamura

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70 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1310-1317
Number of pages8
JournalJournal of Immunology
Volume153
Issue number3
Publication statusPublished - 1994 Aug 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Ishii, N., Asao, H., Kimura, Y., Takeshita, T., Nakamura, M., Tsuchiya, S., Konno, T., Maeda, M., Uchiyama, T., & Sugamura, K. (1994). Impairment of ligand binding and growth signaling of mutant IL-2 receptor γ-chains in patients with X-linked severe combined immunodeficiency. Journal of Immunology, 153(3), 1310-1317.