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A monoclonal antibody directed against an autoimmune epitope on the human beta1-adrenergic receptor recognized in idiopathic dilated cardiomyopathy

Item Type:Article
Title:A monoclonal antibody directed against an autoimmune epitope on the human beta1-adrenergic receptor recognized in idiopathic dilated cardiomyopathy
Creators Name:Mobini, R. and Fu, M. and Wallukat, G. and Magnusson, Y. and Hjalmarson, A. and Hoebeke, J.
Abstract:A monoclonal antibody (MAb M16) was obtained by immunizing Balb/C mice with free peptide H26R, corresponding to the second extracellular loop of the human {beta}1-adrenergic receptor ({beta}1AR), against which functional autoantibodies have been detected in patients with idiopathic dilated cardiomyopathy. The MAb was found to be of IgG2b type and directed against a conformational epitope, encompassing the sequence recognized by the human autoantibodies. BIAcore measurements yielded an equilibrium constant of 6.5 x 107 M1 with an association rate constant (k(on)) of 6.5 x 104 M-1 sec- 1 and a dissociation rate constant (k(off)) of 1.0 x 10-3 sec-1. It immunoprecipitated only poorly the solubilized {beta}1AR of Sf9 cell membranes. Functionally, the MAb was capable of not only reducing the number of the maximal binding sites to the {beta}1-adrenergic receptor of transfected Sf9 cell membranes, but also of displaying a positive chronotropic effect on cultured neonatal rat cardiomyocytes. These properties, which the MAb shares with the human autoantibodies, makes it an interesting tool for passive transfer studies in mice
Keywords:Amino Acid Sequence, Antibody Affinity, Autoantigens, Beta-1 Adrenergic Receptors, Cultured Cells, Dilated Cardiomyopathy, Epitope Mapping, Heart Rate, Hybridomas, Immunoglobulin G, Inbred BALB C Mice, Molecular Sequence Data, Monoclonal Antibodies, Myocardium, Newborn Animals, Peptides, Precipitin Tests, Spodoptera, Transfection, Wistar Rats, Animals, Mice, Rats
Source:Hybridoma
ISSN:0272-457X
Publisher:Mary Ann Liebert (U.S.A.)
Volume:19
Number:2
Page Range:135-142
Date:1 April 2000
Official Publication:https://doi.org/10.1089/02724570050031176
PubMed:View item in PubMed

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