TCRζ chain lacking exon 7 in two patients with systemic lupus erythematosus

To address the molecular mechanism underlying the functional defects of peripheral T cells in systemic lupus erythematosus (SLE), we focused on early signaling events. We demonstrated that protein expression of the TCR zeta chain was significantly decreased in peripheral T cells from patients with SLE compared to normal controls and patients with systemic sclerosis (SSc), Among those patients showing decreased TCR zeta chain expression, we found two patients with pronounced TCR zeta chain abnormalities, including an aberrant 14 kDa form in one and only trace expression in the other. RT-PCR, SSCP and subsequent cloning of the transcripts revealed that bases 468-503, corresponding to exon 7, were deleted in both patients. Since exon 7 spans the GTP/GDP binding site and N-terminal tyrosine in the third ITAM domain of TCR zeta chain, the transcript lacking exon 7 may be responsible for altered signal transduction via TCR in these SLE patients.