title: Studies on the antigenic determinants in the self-association of IgG rheumatoid factor.
abstract: The number, location, and other characteristics of the antigenic determinants for self-association of IgG-rheumatoid factors (IgG-RF) were examined using the IgG-RF isolated from the plasma of one patient as a model system. Affinity chromatography was employed for isolation of the IgG-RF. Sedimentation equilibrium ultracentrifugation was used to study the various interactions. The antigenic valence of IgG-RF Fc, normal human Fc, and rabbit Fc fragments was two for the interaction with Fab fragments from IgG-RF, as might be expected from the molecular symmetry of IgG. The antigenic valence of intact normal IgG, however, was only one, indicating that when one of the available antigenic determinants interacted with the Fab fragment of IgG-RF, the other determinant becomes sterically inaccessible. Reduction and alkylation, known to increase the flexibility of the hinge region, did not alter the antigenic valence of IgG for Fab fragments of IgG-RF. The antigenic valence of IgG-RF in self-association could not be experimentally determined but must be two to permit the observed concentration-dependent further polymer formation of IgG-RF dimers. Unique antigenic determinants on the Fc fragments of IgG-RF were sought and not found, thus reaffirming the formation of two antigen-antibody bonds as the basis for dimerization of IgG-RF molecules. The pFc' and Fc' fragments, representing Cgamma3 domains of IgG, failed to show significant interaction with Fab fragments of IgG-RF, indicating that the antigenic determinants were not expressed by the Cgamma3 regions but are located either on Cgamma2 region or require intact Cgamma2 and Cgamma3 regions for expression. These conclusions were corroborated by the antigenic valence of one for the Fc(i) fragment, a new papain-generated intermediate fragment of Fc, composed of two intact Cgamma3 domains and one intact Cgamma2 domain. Normal IgG, because of its valence of one for interaction with IgG-RF, would effectively terminate further polymerization of IgG-RF dimers. This may well in part explain the finding of smaller IgG-RF complexes in the serum than in synovial fluid of patients with rheumatoid arthritis.
mesh_terms: D000478:Alkylation; D000818:Animals; D000939:Epitopes; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008970:Molecular Weight; D009439:Neuraminidase / Q000494:pharmacology; D010084:Oxidation-Reduction; D011817:Rabbits; D012217:Rheumatoid Factor / Q000276:immunology*
chemical_list: D000939:Epitopes; D007074:Immunoglobulin G; D012217:Rheumatoid Factor; D009439:Neuraminidase