Epitope mapping of human thyroglobulin. Heterogeneous recognition by thyroid pathologic sera.
Thyroglobulin is the major Ag of the thyroid gland involved in autoimmune pathologies. Epitope mapping was carried out with a rabbit polyclonal immune serum against fusion proteins expressed in prokaryotic cells. After screening of an initial human thyroglobulin cDNA library and subcloning of immunoreactive clones, seven epitopes were characterized and localized on the human thyroglobulin monomeric molecule. One was close to each extremity of the molecule, and five others were concentrated in the middle, covering a sixth of this 2748-amino-acid chain. The immunoreactivities of 18 autoimmune sera from different thyroid pathologies were tested against the seven previously characterized epitopes. Those from Hashimoto's thyroiditis were the most immunoreactive. Immune responses were heterogeneous for sera from different pathologies as well as for those from the same pathology. The central epitopes and the near-C-terminal epitope, however, were the epitopes most often recognized by the immune sera. These findings show that some autoepitopes overlap accurately with some heteroepitopes characterized by a polyclonal immune serum directed against the mature protein.
Laboratoire de Biochimie Médicale, INSERM Unité 38, Faculté de Médecine, Marseille, France.
M
M
Henry
Y
Y
Malthièry
E
E
Zanelli
B
B
Charvet
D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D004247:DNA / Q000032:analysis; D000939:Epitopes / Q000032:analysis*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D011817:Rabbits; D013954:Thyroglobulin / Q000235:genetics / Q000276:immunology*; D013959:Thyroid Diseases / Q000276:immunology*; D013964:Thyroid Neoplasms / Q000276:immunology
D000939:Epitopes; D010446:Peptide Fragments; D004247:DNA; D013954:Thyroglobulin