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MODERN RHEUMATOLOGY Vol.12 No.2
>MR12-2
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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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