Antigenic domains on the human thyroglobulin molecule recognized by autoantibodies in patients' sera and by natural autoantibodies isolated from the sera of healthy subjects.

We determined the regions on the human thyroglobulin (hTg) molecule recognized by anti-hTg autoantibodies (aAbs) in the sera of patients with Hashimoto's thyroiditis, Graves' disease, and thyroid carcinoma and by anti-hTg natural aAbs isolated from the sera of healthy subjects. Fifteen anti-hTg monoclonal antibodies (MAbs) directed against six distinct antigenic regions were used for this study. The anti-hTg aAbs in the patients' sera recognized mainly region II and occasionally region IV. The natural aAbs were present in the serum at low concentrations; consequently, we isolated and concentrated them for this investigation. The isolated natural aAbs inhibited the interaction of the anti-hTg MAbs with the majority of the antigenic regions identified. Region II was not well recognized, however, by these natural aAbs. This difference in specificity between the anti-hTg aAbs and the anti-hTg natural aAbs may have diagnostic significance.