Immunogenic and antigenic epitopes of immunoglobulins. XVII--Monoclonal antibodies reactive with common and restricted idiotopes to the heavy chain of human rheumatoid factors

Abstract

Two mouse hybridoma antibodies, G6 and H1, with specificity for idiotypic determinants on the heavy chain of human IgM-RF have been produced. Idiotopes recognized by G6 and H1 were expressed on 5/12 and 2/12 RF paraproteins from the Wa idiotype group respectively, but not on paraproteins lacking rheumatoid factor (RF) activity. Inhibition experiments demonstrated that G6 and H1-specific epitopes were located on (or close to) the antibody binding site of RFs, and measurable on the heavy chain but not their light chains. However, it was concluded that the quaternary structure of the antibody-binding site was important for the optimal expression of both idiotopes. The idiotope recognized by G6 was also detected on polyclonal RFs in unfractionated sera from 8/14 patients with rheumatoid arthritis (RA). The results suggest that the G6 idiotope is a highly conserved determinant on the antibody-binding site of RF. These monoclonal antibodies will allow characterization of RF clonality in RA.