DOMAIN-SPECIFIC ANTI-IGE ANTIBODIES INTERFERE WITH IGE BINDING TO FC-EPSILON-RII

Human anti-IgE autoantibodies have been identified and implicated in t he regulation of IgE-mediated reactions and IgE synthesis. In order to study the potential regulatory role of anti-IgE antibodies on IgE bin ding to the Fc epsilon RII we used a panel of IgE-specific monoclonal antibodies that were mapped by Western blotting against a series of re combinant e domain peptides. Antibodies specific for all E domains wer e detected except those against C epsilon H1. Using a competitive inhi bition cell-binding assay on Fc epsilon RII + 8866 cells, we identifie d two major patterns of anti-IgE activity. Antibodies specific for the C epsilon H3 domain removed IgE whereas those specific for the C epsi lon H2 domain enhanced IgE binding to the Fc epsilon RII. The anti-C e psilon H2 antibodies, in contrast to the anti-C epsilon H3 antibodies, could not dissociate cell-bound IgE from the Fc epsilon RII. Using pr eformed immune complexes of IgE and anti-IgE antibodies, it was clear that the anti-C epsilon H2 antibodies bound more IgE to the Fc epsilon RII by addition of immune complexes to the cell surface. Our results suggest that the opposing actions of either inhibition or enhancement of IgE binding by anti-IgE antibodies are related to their E domain sp ecificity.