IMMUNE RECOGNITION OF HORMONOGENIC SITES OF HUMAN THYROGLOBULIN - STUDIES OF GRAVES SERA AND A MURINE MONOCLONAL-ANTIBODY WITH THYROID-HORMONE ANTIBODY-ACTIVITY

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 I-127 or I-125. I-127-labeled peptides were tested for their ability to displace I-125-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). I-125-labeled peptides were tested for the direct binding to the aforementioned antibodies. None of the peptides displaced I-125-T4 binding to THAA or to a mAb, or exhibited increased binding to THAA and to a mAb. I-125-T4 binding to a mAb was equally displaced by hTgs obtained from a normal thyroid gland (NTg) and a case of Hurthle cell adenoma with undetectable iodine content (CTg). I-125-T, binding to serum gamma globulin in each patient's serum was completely displaced by NTg, but CTg displaced I-125-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.