A common idiotope on human rheumatoid factors identified by a hybridoma antibody.
Human monoclonal and polyclonal anti-IgG autoantibodies [rheumatoid factors (RFs)] are composed primarily of kappa light chains, and may display cross-reactive idiotypes. However, the nature of the shared idiotope(s) has remained unclear. We have prepared a murine hybridoma antibody (17-109) that recognizes an idiotope present on 30% (3/10) of human IgM-RF paraproteins, and absent on immunoglobulins without RF activity. The idiotope was measurable on isolated, intact kappa light chains, but not on light-chain tryptic peptides, nor on isolated heavy chains. A comparison of the binding to 17-109 of five IgM-RF paraproteins, with known kappa chain amino acid sequences, suggested a relationship between the idiotope recognized by the hybridoma and the complementarity-determining regions. The serum of patients with rheumatoid arthritis contained idiotope positive material that bound specifically to a 17-109 immunoadsorbent column. Moreover, the 17-109 anti-idiotope antibody partially inhibited the binding to IgG of IgM-RF and IgA-RF in serum, but did not effect the binding to antigen of IgM and IgA anti-tetanus toxoid antibodies. These results suggest that a significant proportion of IgM-RF paraproteins share an idiotope located at or near the complementarity-determining regions of the kappa light chain. Human serum RFs include a kappa light chain family that is idiotopically related to the kappa chains on IgM-RF paraproteins.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D001667:Binding, Competitive; D003429:Cross Reactions; D000939:Epitopes / Q000032:analysis*; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D012217:Rheumatoid Factor / Q000276:immunology*; D014357:Trypsin
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D012217:Rheumatoid Factor; D014357:Trypsin