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

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 zeta) was significantly decreased in SLE T cells and that two SLE patients exhibited a 36 bp, exon 7 deletion of the TCR zeta mRNA. To investigate further common mutations in TCR zeta 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 zeta cDNA was amplified by RT-PCR. Five out of the eight SLE patients exhibited abnormal migration patterns of the TCR zeta 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 zeta 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 zetaThus, these mutations in TCR zeta mRNA could be responsible for the decreased expression of the TCR zeta protein in SLE T cells.

journal_name

J Autoimmun

journal_title

Journal of autoimmunity

authors

Tsuzaka K,Takeuchi T,Onoda N,Pang M,Abe T

doi

10.1006/jaut.1998.0223

subject

Has Abstract

pub_date

1998-10-01 00:00:00

pages

381-5

issue

5

eissn

0896-8411

issn

1095-9157

pii

S0896-8411(98)90223-2

journal_volume

11

pub_type

杂志文章

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