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

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)381-385
Number of pages5
JournalJournal of Autoimmunity
Volume11
Issue number5
DOIs
Publication statusPublished - 1998 Oct
Externally publishedYes

Fingerprint

T-Cell Antigen Receptor
Systemic Lupus Erythematosus
T-Lymphocytes
Messenger RNA
Mutation
Complementary DNA
Systemic Scleroderma
Polymerase Chain Reaction
Immunoreceptor Tyrosine-Based Activation Motif
Clone Cells
Single-Stranded Conformational Polymorphism
Pathologic Processes
Amino Acid Substitution
Guanosine Triphosphate
Autoimmune Diseases
Tyrosine
Exons
Blood Cells
Binding Sites
Phosphorylation

Keywords

  • Autoimmune disease
  • Mutation
  • Systemic lupus erythematosus
  • T cell receptor
  • TCR ζ chain

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Mutations in T cell receptor ζ chain mRNA of peripheral T cells from systemic lupus erythematosus patients. / Tsuzaka, Kensei; Takeuchi, Tsutomu; Onoda, Natsuko; Pang, Ming; Tohru, Abe.

In: Journal of Autoimmunity, Vol. 11, No. 5, 10.1998, p. 381-385.

Research output: Contribution to journalArticle

Tsuzaka, Kensei ; Takeuchi, Tsutomu ; Onoda, Natsuko ; Pang, Ming ; Tohru, Abe. / Mutations in T cell receptor ζ chain mRNA of peripheral T cells from systemic lupus erythematosus patients. In: Journal of Autoimmunity. 1998 ; Vol. 11, No. 5. pp. 381-385.
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