Interaction of Human IgE with Soluble Forms of IgE High Affinity Receptors

Abstract

Purpose. Interaction of human IgE with its high affinity receptor (FcεRI) on mast cells and basophils is an important step for initiating IgE mediated immune responses. To characterize the IgE and FcεRI interaction, we investigated this interaction in terms of stoichiometry and binding affinity in solution. The binding of IgE and IgE FcεRI α chain, the extracellular portion of IgE high affinity receptor (sFcεRIα) was compared with the binding of IgE and IgE immunoadhesin (FcεRIα-IgG).

Methods. The interaction was characterized by analytical ultracentrifugation, size exclusion chromatography, light scattering and ELISA.

Results. We show that the sFcεRIα is only able to bind to one IgE, while the immunoadhesin can bind to two IgE. The interaction between IgE and FcεRI is very strong. Both forms of soluble receptors have similar intrinsic binding affinity with IgE.

Conclusions. Both soluble receptors (FcεRIα-IgG and sFcεRIα) can block the binding of IgE to its high affinity receptors on cell surface. The FcεRIα-IgG is a better IgE binding protein than sFcεRIα at physiological relevant conditions. A humanized anti-IgE monoclonal antibody, rhuMAb E25 that also can block the binding of IgE to its high affinity receptors appears to bind to IgE at slightly different regions or in a different manner as the soluble forms of IgE receptors.