Mutations in T cell receptor ζ chain mRNA of peripheral T cells from systemic lupus erythematosus patients

Kensei Tsuzaka, Tsutomu Takeuchi, Natsuko Onoda, Ming Pang, Abe Tohru

研究成果: Article査読

47 被引用数 (Scopus)

抄録

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown aetiology. Although it has been reported that T cells might be responsible for the pathogenesis of SLE, it remains unclear whether immune aberrations of SLE T cells are the primary event in this pathological process. We have recently reported that tyrosine phosphorylation and expression of the T cell receptor zeta chain (TCR ζ) was significantly decreased in SLE T cells and that two SLE patients exhibited a 36 bp, exon 7 deletion of the TCR ζ mRNA. To investigate further common mutations in TCR ζ mRNA among SLE patients, mRNA was isolated from the peripheral blood T cells of two normal controls, two systemic sclerosis (SSc) patients, and eight SLE patients. TCR ζ cDNA was amplified by RT-PCR. Five out of the eight SLE patients exhibited abnormal migration patterns of the TCR ζ cDNA in PCR single stranded conformational polymorphism analysis. PCR products were ligated into pUC18 and five clones obtained were sequenced. Analysis of the nucleotide sequences revealed that all of the five pUC18 clones from the normal controls and SSc patients had the normal nucleotide sequence, whereas all eight SLE patients had mutations in TCR ζ cDNA accompanied by predicted amino acid substitutions. Mutations found in six of these patients corresponded to those of the third immunoreceptor tyrosine-based activation motif (ITAM) domain or the GTP/GDP binding site in TCR ζ. Thus, these mutations in TCR ζ mRNA could be responsible for the decreased expression of the TCR ζ protein in SLE T cells.

本文言語English
ページ(範囲)381-385
ページ数5
ジャーナルJournal of Autoimmunity
11
5
DOI
出版ステータスPublished - 1998 10
外部発表はい

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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