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MR Vol.12 No.2 indexに戻る
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MODERN RHEUMATOLOGY
Vol.12 No.2 |
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T-cell receptor + mRNA with an alternatively
spliced 3' untranslated region is generated predominantly in the
peripheral blood T cells of systemic lupus erythematosus patients |
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| K. Tsuzaka1, N. Onoda1, K. Yoshimoto1,
Y. Setoyama1, K. Suzuki1, M. Pang1, T. Abe1, T. Takeuchi1 |
| (1) Second Department of Internal Medicine, Saitama
Medical Center, Saitama Medical School, 1981 Kamoda, Kawagoe 350-8550,
Japan |
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| Abstract |
| Abstract To investigate the mechanism of the
downregulation of T-cell receptor + chain (TCR+) expression in the
peripheral blood T cells (PBTs) of systemic lupus erythematosus (SLE)
patients, we analyzed the 3' untranslated region (3'UTR) of TCR+
mRNA, because the 3'UTR in mRNA is responsible for posttranscriptional
regulation. Use of the reverse transcriptase polymerase chain reaction
(RT-PCR) to amplify the 917 bp TCR+ 3'UTR cDNA demonstrated that
the short variant cDNA (355 bp), expressed as an alternatively spliced
3'UTR with 562-bp deletion, was predominated in the PBTs of 11 of
14 SLE patients, whereas mainly the wild-form cDNA (917 bp) was detected
in the PBTs of seven negative controls (two systemic sclerosis patients,
five normal controls) and in two T-cell line hybridomas. Semiquantitative
PCR also revealed the predominant expression of the TCR+ mRNA with
alternatively spliced 3'UTR (TCR+ mRNA/as-3'UTR), and a decreased
expression of TCR+ mRNA with the wild form 3'UTR (TCR+ mRNA/w-3'UTR)
in SLE T cells. However, there was no difference in the expression
of the open reading frame (ORF) TCR+ mRNA between the negative controls
and SLE patients. The TCR+ protein expression level according to
Western blot analysis correlated well with that of TCR+ mRNA/w-3'UTR
(r = 0.931) and reversibly with TCR+ mRNA/as-3'UTR (r = m0.614),
but not with ORF TCR+ mRNA (r = m0.296). It can be concluded that
the reduced expression of TCR+ mRNA/w-3'UTR and the predominant expression
of TCR+ mRNA/as-3'UTR lead to downregulation of the TCR+ protein
in SLE T cells. |
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| Key words |
| Key words Alternative splicing ・ Autoimmune
disease ・ CD3 ・ Signal transduction ・ T lymphocytes |
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