Fc epitopes for human rheumatoid factors and the relationships of rheumatoid factors to the Fc binding proteins of microorganisms

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.