Takeuchi T, Tsuzaka K, Pang M, Amano K, Koide J, Abe T
Department of Internal Medicine, Saitama Medical Center, Saitama Medical School, Kawagoe, Japan.
Int Immunol. 1998 Jul;10(7):911-21. doi: 10.1093/intimm/10.7.911.
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 468503, 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.
为了探究系统性红斑狼疮（SLE）外周血T细胞功能缺陷的分子机制，我们聚焦于早期信号事件。我们发现，与正常对照和系统性硬化症（SSc）患者相比，SLE患者外周血T细胞中TCR ζ链的蛋白表达显著降低。在那些TCR ζ链表达降低的患者中，我们发现两名患者存在明显的TCR ζ链异常，其中一名患者出现异常的14 kDa形式，另一名患者仅有微量表达。RT-PCR、SSCP及随后的转录本克隆显示，两名患者均缺失对应于外显子7的468503位碱基。由于外显子7跨越TCR ζ链第三个免疫受体酪氨酸激活基序（ITAM）结构域中的GTP/GDP结合位点和N端酪氨酸，缺失外显子7的转录本可能导致这些SLE患者中TCR信号转导改变。
