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 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.
Sakata
S
S
Third Department of Internal Medicine, Gifu University School of Medicine, Japan.
Matsuda
M
M
Takuno
H
H
Ogawa
T
T
Matsui
I
I
Sarui
H
H
Maekawa
H
H
Kotani
T
T
Okuda
K
K
Tarutani
O
O
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood; D001667:Binding, Competitive; D000939:Epitopes; D006111:Graves Disease / Q000097:blood / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology; D013954:Thyroglobulin / Q000097:blood / Q000276:immunology*; D013963:Thyroid Hormones / Q000097:blood / Q000276:immunology; D013974:Thyroxine / Q000097:blood / Q000276:immunology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D000939:Epitopes; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D013963:Thyroid Hormones; D013954:Thyroglobulin; D013974:Thyroxine