title: Molecular model, calcium sensitivity, and disease specificity of a conformational thyroperoxidase B-cell epitope.
abstract: While studying the humoral mechanisms involved in thyroid autoimmunity, we located a B-cell autoepitope in the extracellular C-terminal region of human thyroperoxidase. Structural modeling showed that this region encompasses both a Sushi-like and an epidermal growth factor-like domain, the flexible arrangement of which was putatively stabilized by calcium. The recombinant peptide was found to contain the previously identified conformational thyroperoxidase autoepitope. The occurrence of a calcium-induced conformational change was confirmed using a recombinant peptide monoclonal antibody, the decrease of which in binding to calcium-saturated thyroperoxidase was reversed by a chelating agent. The disease specificity of recombinant peptide, which was more frequently recognized by Hashimoto's than by Graves' patients, adds to its potential value as a diagnostic and preventive tool in the context of B-cell autoimmunity.
authors.affiliation: U 38 INSERM/Laboratoire de Biochimie Endocrinienne et Métabolique, Faculté de Médecine Timone, Université de la Méditerranée, 13385 Marseille Cedex 05, France.
authors.forename: V
authors.initials: V
authors.lastname: Estienne
authors.forename: C
authors.initials: C
authors.lastname: Blanchet
authors.forename: P
authors.initials: P
authors.lastname: Niccoli-Sire
authors.forename: C
authors.initials: C
authors.lastname: Duthoit
authors.forename: J M
authors.initials: JM
authors.lastname: Durand-Gorde
authors.forename: C
authors.initials: C
authors.lastname: Geourjon
authors.forename: D
authors.initials: D
authors.lastname: Baty
authors.forename: P
authors.initials: P
authors.lastname: Carayon
authors.forename: J
authors.initials: J
authors.lastname: Ruf
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D001324:Autoantigens / Q000737:chemistry*; D001402:B-Lymphocytes / Q000276:immunology*; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D000939:Epitopes / Q000737:chemistry*; D006111:Graves Disease / Q000276:immunology*; D006801:Humans; D007453:Iodide Peroxidase / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation / Q000187:drug effects; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013967:Thyroiditis, Autoimmune / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D001324:Autoantigens; D000939:Epitopes; D011994:Recombinant Proteins; D007453:Iodide Peroxidase; D002118:Calcium