Characterization of complex formation by humanized anti-IgE monoclonal antibody and monoclonal human IgE

J Liu, P Lester, S Builder, SJ Shire - Biochemistry, 1995 - ACS Publications
J Liu, P Lester, S Builder, SJ Shire
Biochemistry, 1995ACS Publications
Revised Manuscript Received May 8, 1995® abstract: The interaction of human IgE with
high-affinity IgE Fc receptors on cells of the immune system plays an essential rolein the
type I hypersensitivity reaction. A proposed therapyis to use an anti-IgE monoclonal antibody
to block the binding of IgE to its high-affinity receptor on mast cells and basophils, thus
preventing subsequent release of the inflammatory agents after exposure to allergen. We
report here the solution characteristics of immune complexes formed by a humanized anti …
Revised Manuscript Received May 8, 1995® abstract: The interaction of human IgE with high-affinity IgE Fc receptors on cells of the immune system plays an essential rolein the type I hypersensitivity reaction. A proposed therapyis to use an anti-IgE monoclonal antibody to block the binding of IgE to its high-affinity receptor on mast cells and basophils, thus preventing subsequent release of the inflammatory agents after exposure to allergen. We report here the solution characteristics of immune complexes formed by a humanized anti-IgE monoclonal antibody (rhuMAb E25) and IgE using sedimentation analysisand size exclusion chromatography. We demonstrate that the rhuMAb E25 is able to form a variety of complexes with IgE at different molar ratios. The largest complex was identified by sedimentation equilibrium analysis as a heterohexamer with very high stability. The intermediate complex formed when one of the interacting components is in large molar excess appears to have a trimeric structure. The high-affinity interaction of rhuMAb E25 and IgE has also been confirmed. Furthermore, by using hydrodynamic modeling, we show that the largest complex may be representedby a cyclic structure.
Human IgE plays a central role in type I hypersensitivity reactions, such as asthma, eczema, and hay fever. Following the initial contact with allergen, the local B cells, stimulated by the signal from the antigen-presenting cells and Th cells, recognize the appropriate epitopes via specific cell surface receptors and produce specific IgE antibodies. These antibodies bind to the high-affinity Fc receptors (FceRI)'on
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