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, 25 92-2603 and HTg-6, 2737-2748) and two peptides (HTg-3, 2582-2591 and H Tg-5, 2687-2694) with or without hormonogenic acceptor tyrosine of hum an 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 b inding to thyroid hormone autoantibodies (THAA) in two cases of Graves ' disease and to a murine anti-hTg monoclonal antibody with anti-T4 ac tivity (mAb). I-125-labeled peptides were tested for the direct bindin g to the aforementioned antibodies. None of the peptides displaced I-1 25-T4 binding to THAA or to a mAb, or exhibited increased binding to T HAA and to a mAb. I-125-T4 binding to a mAb was equally displaced by h Tgs obtained from a normal thyroid gland (NTg) and a case of Hurthle c ell adenoma with undetectable iodine content (CTg). I-125-T, binding t o serum gamma globulin in each patient's serum was completely displace d by NTg, but CTg displaced I-125-T4 binding 2% and 5% in Case 1 and C ase 2, respectively. It was speculated that the mAb recognizes a topol ogical epitope around the hormonogenic site of hTg, while that of THAA in our two cases recognizes only T4 or an iodine dependent topologica l epitope(s) of hTg.