title: Identification of an immunodominant region recognized by human autoantibodies in a three-dimensional model of thyroid peroxidase.
abstract: Autoimmune thyroid diseases (AITD) are characterized by the presence of autoantibodies to thyroid peroxidase (TPO). This response is dominated by autoantibodies to two conformational determinants, termed A and B, that have been defined by monoclonal antibodies but whose structures and location within TPO are unknown. We have modeled the three-dimensional structure of the extracellular region of TPO, raised antisera to prominent surface structures, and identified an epitope that we show to be a critical part of the B determinant. Antibodies to this epitope inhibit the binding to TPO of human autoantibodies in virtually all serum samples from 65 patients with AITD that were tested. This first description of a model of the three-dimensional structure and location of a major autoantigenic determinant within the TPO molecule may provide structural clues for identifying causative agents or developing novel therapeutic strategies.
authors.affiliation: The Randall Centre and Guy's, King's and St. Thomas' School of Medicine, King's College London, United Kingdom.
authors.forename: P
authors.initials: P
authors.lastname: Hobby
authors.forename: A
authors.initials: A
authors.lastname: Gardas
authors.forename: R
authors.initials: R
authors.lastname: Radomski
authors.forename: A M
authors.initials: AM
authors.lastname: McGregor
authors.forename: J P
authors.initials: JP
authors.lastname: Banga
authors.forename: B J
authors.initials: BJ
authors.lastname: Sutton
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D001666:Binding Sites, Antibody; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D016056:Immunodominant Epitopes / Q000737:chemistry* / Q000276:immunology; D007453:Iodide Peroxidase / Q000737:chemistry* / Q000276:immunology*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010446:Peptide Fragments / Q000737:chemistry; D010449:Peptide Mapping; D011817:Rabbits; D016415:Sequence Alignment
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007106:Immune Sera; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D007453:Iodide Peroxidase