Nardella F A, Oppliger I R, Stone G C, Sasso E H, Mannik M, Sjöquist J, Schröder A K, Christensen P, Johansson P J, Björck L
Division of Rheumatology, University of Washington, Seattle 98195.
Scand J Rheumatol Suppl. 1988;75:190-8. doi: 10.3109/03009748809096761.
Work from our laboratories has shown that the major antigenic determinants for rheumatoid factors (RFs) are in the C gamma 2-C gamma 3 interface region of IgG in the same area that binds staphylococcal protein A (SPA). Furthermore, the Fc binding proteins of groups A, C and G streptococci as well as the Fc binding proteins induced on cell surfaces by herpes simplex virus type I also bind to the same area of IgG. These binding site similarities between RFs and the microbial Fc binding proteins suggested conformational similarities between the RF antigen combining regions and the Fc binding regions of the microbial proteins. This hypothesis was supported by the observation that antibodies to SPA bind to the antigen combining regions of most RFs as well as to the Fc binding region of the T15 group A streptococcal Fc binding protein. These findings indicate that RFs bear the conformational internal image of these microbial proteins and suggest that RFs could arise as antibodies to the idiotypic determinants on antibodies to microbial Fc binding proteins. Alternatively, microbial Fc binding proteins could present IgG to the immune system in a way that renders specific areas of the C gamma 2-C gamma 3 interface region immunogenic. These relationships between RFs and microbial Fc binding proteins may prove to be important for our understanding of the generation of RFs in rheumatoid arthritis.
我们实验室的研究表明，类风湿因子（RFs）的主要抗原决定簇位于IgG的Cγ2-Cγ3界面区域，该区域与葡萄球菌蛋白A（SPA）的结合区域相同。此外，A、C和G组链球菌的Fc结合蛋白以及I型单纯疱疹病毒在细胞表面诱导产生的Fc结合蛋白也与IgG的同一区域结合。RFs与微生物Fc结合蛋白之间的这些结合位点相似性表明，RF抗原结合区域与微生物蛋白的Fc结合区域在构象上具有相似性。这一假设得到了以下观察结果的支持：SPA抗体可与大多数RFs的抗原结合区域以及T15组A链球菌Fc结合蛋白的Fc结合区域结合。这些发现表明，RFs具有这些微生物蛋白的构象内影像，并提示RFs可能作为针对微生物Fc结合蛋白抗体上独特型决定簇的抗体而产生。或者，微生物Fc结合蛋白可能以某种方式将IgG呈递给免疫系统，使Cγ2-Cγ3界面区域的特定区域具有免疫原性。RFs与微生物Fc结合蛋白之间的这些关系可能对我们理解类风湿关节炎中RFs的产生具有重要意义。
