Fine specificity of the IgE interaction with the low and high affinity Fc receptor.
The characterization of the site(s) on the IgE molecule that accommodate the high (Fc epsilon RI) and low (Fc epsilon RII) affinity receptors for IgE should allow the design of IgE analogues that can be used to block the onset of the allergic response or to regulate IgE production. To identify the IgE domain responsible for receptor binding, we generated a series of chimeric IgE antibodies in which constant region domains were interchanged between the human and mouse molecules. Binding studies with these chimeras revealed that both the high and low affinity receptor binding-sites reside primarily in the third constant domain of IgE (C epsilon 3). Additional chimeric IgE molecules were generated in which different parts of the human C epsilon 3 domain were exchanged with their murine homologues. Binding experiments with these chimeras suggest that not only the sequence of a particular C epsilon 3 fragment, but the entire C epsilon 3 domain in its native configuration is essential for binding to the Fc epsilon RI. The amino acid residues determining the species specificity of the Fc epsilon RII are not contained in the first 16 amino acids of the C epsilon 3 domain.
Nissim
A
A
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Schwarzbaum
S
S
Siraganian
R
R
Eshhar
Z
Z
D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D000939:Epitopes; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D066298:In Vitro Techniques; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013045:Species Specificity; D014162:Transfection
D000911:Antibodies, Monoclonal; D000939:Epitopes; D009838:Oligodeoxyribonucleotides; D017455:Receptors, IgE; D011993:Recombinant Fusion Proteins; D007073:Immunoglobulin E