Misaki Y, Yamamoto K, Yanagi K, Miura H, Ichijo H, Kato T, Mato T, Welling-Wester S, Nishioka K, Ito K
Department of Medicine and Physical Therapy, Faculty of Medicine, University of Tokyo, Japan.
Eur J Immunol. 1993 May;23(5):1064-71. doi: 10.1002/eji.1830230513.
The mechanism of autoantibody production in autoimmune diseases is not well understood. In the present study we performed the B cell epitope mapping of the U1 small nuclear ribonucleoprotein (snRNP)-C, one of the target molecules of anti-nRNP autoantibody to investigate how B cells respond to the autoantigen. After cloning and expression of a full length complementary DNA (cDNA) encoding the U1-C protein, several truncated mutants of the cDNA were constructed and expressed in E. coli. Although a few epitopes were distributed on the whole molecule, all anti-C protein antibody-positive patients' sera tested recognized the region between amino acid residues 102 and 125 of the coding sequence. This universal epitope region contains an amino acid sequence similar to that of the herpes simplex virus type 1 ICP4 protein. The peptides representing each molecule were cross-reactive to each other. In addition this region cross-reacted to the B/B' protein. These observations suggest that molecular mimicry might be involved in the initiation of autoantibody production, followed by cross-reactive events between the autoantigens and by antigen-driven mechanisms to generate more complicated autoantibody patterns against the U1 snRNP complexes.
自身免疫性疾病中自身抗体产生的机制尚未完全明确。在本研究中，我们对U1小核糖核蛋白（snRNP）-C进行了B细胞表位作图，U1-C是抗nRNP自身抗体的靶分子之一，目的是研究B细胞如何对抗原产生反应。在克隆并表达编码U1-C蛋白的全长互补DNA（cDNA）后，构建了该cDNA的几个截短突变体并在大肠杆菌中表达。尽管有一些表位分布在整个分子上，但所有检测的抗C蛋白抗体阳性患者血清均识别编码序列中氨基酸残基102至125之间的区域。这个通用表位区域包含一段与单纯疱疹病毒1型ICP4蛋白相似的氨基酸序列。代表每个分子的肽段之间存在交叉反应。此外，该区域与B/B'蛋白也发生交叉反应。这些观察结果表明，分子模拟可能参与了自身抗体产生的起始过程，随后是自身抗原之间的交叉反应事件，以及抗原驱动机制，从而产生针对U1 snRNP复合物的更复杂的自身抗体模式。
