Interaction of human IgE with soluble forms of IgE high affinity receptors.
OBJECTIVE
Interaction of human IgE with its high affinity receptor (Fc epsilon RI) on mast cells and basophils is an important step for initiating IgE mediated immune responses. To characterize the IgE and Fc epsilon RI interaction, we investigated this interaction in terms of stoichiometry and binding affinity in solution. The binding of IgE and IgE Fc epsilon RI alpha chain, the extracellular portion of IgE high affinity receptor (sFc epsilon RI alpha) was compared with the binding of IgE and IgE immunoadhesin (Fc epsilon RI alpha-IgG).


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


RESULTS
We show that the sFc epsilon RI alpha is only able to bind to one IgE, while the immunoadhesin can bind to two IgE. The interaction between IgE and Fc epsilon RI is very strong. Both forms of soluble receptors have similar intrinsic binding affinity with IgE.


CONCLUSIONS
Both soluble receptors (Fc epsilon RI alpha-IgG and sFc epsilon RI alpha) can block the binding of IgE to its high affinity receptors on cell surface. The Fc epsilon RI alpha-IgG is a better IgE binding protein than sFc epsilon RI alpha 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.
Liu
J
J
Department of Pharmaceutical Research & Development, Genentech, Inc., South San Francisco, California 94080, USA. jliu@gene.com
Ruppel
J
J
Shire
S J
SJ
D000911:Antibodies, Monoclonal / Q000276:immunology; D002850:Chromatography, Gel; D006801:Humans; D007073:Immunoglobulin E / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D008027:Light; D011485:Protein Binding; D017455:Receptors, IgE / Q000737:chemistry / Q000378:metabolism*; D012542:Scattering, Radiation; D012995:Solubility; D014461:Ultracentrifugation
D000911:Antibodies, Monoclonal; D017455:Receptors, IgE; D007073:Immunoglobulin E