CD23 trimers are preassociated on the cell surface even in the absence of its ligand, IgE.
Allergic disease is mediated by high levels of allergen-specific IgE. IgE binding to CD23, the low affinity receptor for IgE, results in a negative feedback signal leading to a decrease in IgE production. Previous studies have shown that CD23 associates as an oligomer and that cooperative binding of at least two lectin domains is required for high affinity IgE binding to CD23. We have previously shown that cooperative binding is required for regulation of IgE production. This study describes the production of several mAbs that bind the stalk region of murine CD23. One of the Abs, 19G5, inhibited the IgE/CD23 interaction at 37 degrees C, but not at 4 degrees C. Analysis of the binding properties of these Abs revealed that CD23 dissociates at high temperatures, such as 37 degrees C; however, the N terminus is constitutively associated, indicating partial, rather than complete, dissociation. A novel finding was that the stalk region, previously thought to mediate trimer association, was not required for oligomerization. These data reveal important information about the structure of CD23 that may be useful in modulating IgE production.
Kilmon
Michelle A
MA
Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Shelburne
Anne E
AE
Chan-Li
Yee
Y
Holmes
Kevin L
KL
Conrad
Daniel H
DH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000494:pharmacology; D001666:Binding Sites, Antibody; D001667:Binding, Competitive / Q000276:immunology; D016466:CHO Cells; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D006224:Cricetinae; D003593:Cytoplasm / Q000276:immunology / Q000378:metabolism; D018985:Epitopes, B-Lymphocyte / Q000276:immunology / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D006825:Hybridomas; D006868:Hydrolysis; D007073:Immunoglobulin E / Q000378:metabolism; D008024:Ligands; D011485:Protein Binding / Q000276:immunology; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism*; D013696:Temperature
D000911:Antibodies, Monoclonal; D018985:Epitopes, B-Lymphocyte; D008024:Ligands; D017455:Receptors, IgE; D007073:Immunoglobulin E