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 3Ј untranslated region (3ЈUTR) of TCR mRNA, because the 3ЈUTR in mRNA is responsible for posttranscriptional regulation. Use of the reverse transcriptase polymerase chain reaction (RT-PCR) to amplify the 917 bp TCR 3ЈUTR cDNA demonstrated that the short variant cDNA (355 bp), expressed as an alternatively spliced 3ЈUTR 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 3ЈUTR (TCR mRNA/as-3ЈUTR), and a decreased expression of TCR mRNA with the wild form 3ЈUTR (TCR mRNA/w-3ЈUTR) 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-3ЈUTR (r ϭ 0.931) and reversibly with TCR mRNA/as-3ЈUTR (r ϭ Ϫ0.614), but not with ORF TCR mRNA (r ϭ Ϫ0.296). It can be concluded that the reduced expression of TCR mRNA/w-3ЈUTR and the predominant expression of TCR mRNA/as-3ЈUTR lead to downregulation of the TCR protein in SLE T cells.