Immune recognition of hormonogenic sites of human thyroglobulin : studies of Grave's sera and a murine monoclonal antibody with thyroid hormone antibody activity

• Published in: Endocrine journal 1993-08, Vol.40 (4), p.393-398
• Main Authors: SAKATA, S, MATSUDA, M, MIURA, K, TAKUNO, H, OGAWA, T, MATSUI, I, SARUI, H, MAEKAWA, H, KOTANI, T, OKUDA, K, TARUTANI, O
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - metabolism; Autoantibodies - blood; Binding, Competitive; Biological and medical sciences; Endocrinopathies; Epitopes; Graves Disease - blood; Graves Disease - immunology; Humans; In Vitro Techniques; Iodine Radioisotopes; Medical sciences; Mice; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Peptide Fragments - immunology; Thyroglobulin - blood; Thyroglobulin - immunology; Thyroid Hormones - blood; Thyroid Hormones - immunology; Thyroid. Thyroid axis (diseases); Thyroxine - blood; Thyroxine - immunology
• ISSN: 0918-8959; 1348-4540
• DOI: 10.1507/endocrj.40.393

We synthesized four peptides (HTg-1, 1-10; HTg-2, 2547-2558; HTg-4, 2592-2603 and HTg-6, 2737-2748) and two peptides (HTg-3, 2582-2591 and HTg-5, 2687-2694) with or without hormonogenic acceptor tyrosine of human thyroglobulin (hTg). They were iodinated with 127I or 125I. 127I-labeled peptides were tested for their ability to displace 125I-T4 binding to thyroid hormone autoantibodies (THAA) in two cases of Graves' disease and to a murine anti-hTg monoclonal antibody with anti-T4 activity (mAb). 125I-labeled peptides were tested for the direct binding to the aforementioned antibodies. None of the peptides displaced 125I-T4 binding to THAA or to a mAb, or exhibited increased binding to THAA and to a mAb. 125I-T4 binding to a mAb was equally displaced by hTgs obtained from a normal thyroid gland (NTg) and a case of Hürthle cell adenoma with undetectable iodine content (CTg). 125I-T4 binding to serum gamma globulin in each patient's serum was completely displaced by NTg, but CTg displaced 125I-T4 binding 2% and 5% in Case 1 and Case 2, respectively. It was speculated that the mAb recognizes a topological epitope around the hormonogenic site of hTg, while that of THAA in our two cases recognizes only T4 or an iodine dependent topological epitope(s) of hTg.