Kato T, Sasakawa H, Suzuki S, Shirako M, Tashiro F, Nishioka K, Yamamoto K
Institute of Medical Science, St. Marianna University School of Medicine, Kanagawa, Japan.
Arthritis Rheum. 1995 Jul;38(7):990-8. doi: 10.1002/art.1780380716.
This study was undertaken to clarify the mechanisms responsible for the generation of anti-52-kd SS-A/Ro autoantibodies and to elucidate why, as has recently been reported, anti-52-kd autoantibodies preferentially recognize the denatured form rather than the native 52-kd molecule.
Using a series of truncated 52-kd autoantigens, produced as beta-galactosidase fusion proteins in Escherichia coli, the B cell epitope distribution was probed with 18 anti-Ro-positive sera by immunoblotting and by enzyme-linked immunosorbent assay.
Nearly all the antigenicity of the molecule was found to be linked to its leucine zipper region. In a further study using 9 of the 18 sera, the antigenicity of the molecule was found to be mainly formed by multiple conformational epitopes, and one of these epitopes appeared to be universally recognized by all the sera tested.
The recognition of multiple epitopes indicates that the Ro 52-kd antigen itself drives the autoimmunity to this molecule. Further, the concentration of the antigenicity at the leucine zipper region may explain why anti-52-kd antibodies preferentially recognize the denatured protein rather than its native form.
进行本研究以阐明产生抗52-kd SS-A/Ro自身抗体的机制，并阐明为何如最近所报道的，抗52-kd自身抗体优先识别变性形式而非天然的52-kd分子。
使用一系列在大肠杆菌中作为β-半乳糖苷酶融合蛋白产生的截短52-kd自身抗原，通过免疫印迹和酶联免疫吸附测定，用18份抗Ro阳性血清探测B细胞表位分布。
发现该分子几乎所有的抗原性都与其亮氨酸拉链区域相关。在使用18份血清中的9份进行的进一步研究中，发现该分子的抗原性主要由多个构象表位形成，并且这些表位之一似乎被所有测试血清普遍识别。
对多个表位的识别表明Ro 52-kd抗原自身驱动针对该分子的自身免疫。此外，抗原性在亮氨酸拉链区域的集中可能解释了为何抗52-kd抗体优先识别变性蛋白而非其天然形式。
