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 huma n 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 thyro peroxidase autoepitope. The occurrence of a calcium-induced conformational change was confirmed using a recombinant peptide monoclonal antibody, the d ecrease of which in binding to calcium-saturated thyroperoxidase was revers ed by a chelating agent. The disease specificity of recombinant peptide, wh ich was more frequently recognized by Hashimoto's than by Graves' patients, adds to its potential value as a diagnostic and preventive tool in the con text of B-cell, autoimmunity.