Molecular model, calcium sensitivity, and disease specificity of a conformational thyroperoxidase B-cell epitope.
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.
Estienne
V
V
U 38 INSERM/Laboratoire de Biochimie Endocrinienne et Métabolique, Faculté de Médecine Timone, Université de la Méditerranée, 13385 Marseille Cedex 05, France.
Blanchet
C
C
Niccoli-Sire
P
P
Duthoit
C
C
Durand-Gorde
J M
JM
Geourjon
C
C
Baty
D
D
Carayon
P
P
Ruf
J
J
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*
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D001324:Autoantigens; D000939:Epitopes; D011994:Recombinant Proteins; D007453:Iodide Peroxidase; D002118:Calcium