Domain-specific anti-IgE antibodies interfere with IgE binding to Fc epsilon RII.
Human anti-IgE autoantibodies have been identified and implicated in the regulation of IgE-mediated reactions and IgE synthesis. In order to study the potential regulatory role of anti-IgE antibodies on IgE binding to the Fc epsilon RII we used a panel of IgE-specific monoclonal antibodies that were mapped by Western blotting against a series of recombinant epsilon domain peptides. Antibodies specific for all epsilon domains were detected except those against C epsilon H1. Using a competitive inhibition cell-binding assay on Fc epsilon RII + 8866 cells, we identified two major patterns of anti-IgE activity. Antibodies specific for the C epsilon H3 domain removed IgE whereas those specific for the C epsilon H2 domain enhanced IgE binding to the Fc epsilon RII. The anti-C epsilon H2 antibodies, in contrast to the anti-C epsilon H3 antibodies, could not dissociate cell-bound IgE from the Fc epsilon RII. Using preformed 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 epsilon domain specificity.
Miescher
S
S
Institute of Clinical Immunology, Inselspital, Berne, Switzerland.
Vogel
M
M
Stämpfli
M R
MR
Wasserbauer
E
E
Kricek
F
F
Vorburger
S
S
Stadler
B M
BM
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex / Q000494:pharmacology; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D007457:Iodine Radioisotopes; D051379:Mice; D011485:Protein Binding / Q000276:immunology; D017455:Receptors, IgE / Q000187:drug effects / Q000378:metabolism*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D007457:Iodine Radioisotopes; D017455:Receptors, IgE; C026408:anti-IgE antibodies; D007073:Immunoglobulin E; D016650:Fluorescein-5-isothiocyanate