Peptides of human thyroglobulin reactive with sera of patients with autoimmune thyroid disease.
Autoantibodies to thyroglobulin (Tg) are a prominent feature of the two autoimmune thyroid diseases, chronic lymphocytic (Hashimoto's) thyroiditis and Graves' disease. Similar autoantibodies are found in the serum of many normal individuals without evidence of thyroid disease. Previous studies have indicated that patients with autoimmune thyroid disease recognize epitopes of Tg which are not usually recognized by normal individuals. The goal of this investigation was to identify peptide fragments of Tg bearing these disease-associated epitopes. For this purpose, we utilized a panel of mAbs that bind to different epitopes of the Tg molecule. One of these mAbs (137C1) reacted with an epitope that was also recognized by the sera of patients with autoimmune thyroiditis. In the present study, we show that two peptides (15 and 23 kDa) that reacted with mAb 137C1 are located in different parts of the Tg molecule. Each peptide inhibited the binding of mAb 137C1 to the other peptide and to the intact Tg, indicating that the same epitope was represented on the two peptides. Loops and helices of the secondary structure of the two peptides might be involved in the conformational epitope recognized by mAb 137C1. A striking finding of this study is that two apparently unrelated fragments of the Tg molecule bind to the same mAb. These findings may have important ramifications with regard to epitope spread and the progression of the autoimmune response to disease.
Saboori
A M
AM
Departments ofPathology and Biophysics and Biophysical Chemistry, School of Medicine, and Department of Molecular Microbiology and Immunology, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
Rose
N R
NR
Yuhasz
S C
SC
Amzel
L M
LM
Burek
C L
CL
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D018604:Epitope Mapping; D006111:Graves Disease / Q000097:blood* / Q000209:etiology; D006801:Humans; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D020539:Sequence Analysis, Protein; D013954:Thyroglobulin / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000097:blood* / Q000209:etiology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D013954:Thyroglobulin