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Structural and functional analysis of the B cell epitopes recognized by anti-receptor autoantibodies in patients with chagas' disease

Item Type:Article
Title:Structural and functional analysis of the B cell epitopes recognized by anti-receptor autoantibodies in patients with chagas' disease
Creators Name:Elies, R. and Ferrari, I. and Wallukat, G. and Lebesgue, D. and Chiale, P. and Elizari, M. and Rosenbaum, M. and Hoebeke, J. and Levin, M.J.
Abstract:IgG fractions of patients were screened for autoantibodies against the beta1- and beta2-adrenoceptors and the M2 acetylcholine receptor by enzyme immunoassays and surface plasmon resonance (SPR) using peptides corresponding to the second extracellular loop of these receptors. A high prevalence of anti-M2 acetylcholine receptor and, in decreasing order, of anti-beta1- and anti-beta2-adrenoceptor autoantibodies was shown. The enzyme immunoassays and the SPR studies on the anti-beta1 adrenoceptor and the M2 acetylcholine receptor autoantibodies were dependent on the ionic strength of the interaction buffer, suggesting the importance of electrostatic interactions in Ab recognition. IgG fractions showed chronotropic effects on neonatal rat cardiomyocytes in vitro. The positive chronotropic effect was enhanced in the presence of 1 microM of atropine, demonstrating a muscarinic stimulation by the IgG fractions in the presence of a beta-adrenergic stimulation, which was blocked by the use of 1 microM of the beta1-selective antagonist bisoprolol. The beta2-selective antagonist ICI 118,551 only partially inhibited the positive chronotropic effect induced by the IgG fractions, confirming the minor functional importance of autoantibodies against the beta2-adrenoceptor. Affinity-purified Abs confirmed that Abs against the beta1-adrenoceptors and the M2 muscarinic receptors exist together with an Ab population recognizing a cross-reactive epitope on both receptors. This epitope could be identified as a polyanionic stretch present in the second extracellular loop of both the beta1-adrenoceptor and the M2 acetylcholine receptor. This stretch corresponds to the previously determined cross-reactive epitope between the P0 ribosomal protein of Trypanosoma cruzi and the beta1-adrenoceptor.
Keywords:Adrenergic beta-Antagonists, Amino Acid Sequence, Autoantibodies, Autoantigens, Autoimmune Diseases, beta-1 Adrenergic Receptors, beta-2 Adrenergic Receptors, Bisoprolol, Chagas Cardiomyopathy, Chagas Disease, Cross Reactions, Epitopes, Immunoglobulin G, Molecular Sequence Data, Muscarinic Receptors, Myocardium, Peptide Fragments, Propanolamines, Animals, Rats
Source:Journal of Immunology
ISSN:0022-1767
Publisher:American Association of Immunologists (U.S.A.)
Volume:157
Number:9
Page Range:4203-4211
Date:1 November 1996
Official Publication:http://www.jimmunol.org/cgi/content/abstract/157/9/4203
PubMed:View item in PubMed

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