Structural features of the autoantigens involved in thyroid autoimmune disease: the thyroid microsomal/microvillar antigen.
The microsomal/microvillar antigen of the human thyroid gland which provokes thyroid autoimmunity was characterised by immunoprecipitation studies. Sera from patients with Hashimoto's thyroiditis, primary myxoedema or Graves' disease containing autoanti-microsomal antibody specifically precipitated a component, which under reducing conditions migrates with a mol. wt of 105,000 on SDS-polyacrylamide gel electrophoresis. This protein was absent in auto- or xeno-anti-thyroglobulin precipitates, which under reducing conditions display four polypeptides of Mr 260,000, 230,000, 180,000 and 142,000. Under non-reducing conditions, the microsomal/microvillar antigen displayed a small shift in mobility to a mol. wt of 117,000 suggesting the presence of intrachain disulphide bonds. In contrast, under these conditions, anti-thyroglobulin precipitated components displaying polypeptides of approx. mol. wts in the region of 240,000-260,000, 170,000-180,000 and 140,000. Absorption of thyroiditis sera on thyroglobulin-Sepharose followed by immunoprecipitation abolished the anti-thyroglobulin components without affecting the binding of the 105,000-dalton polypeptide, if the sera contained antimicrosomal antibody. No comparable material was identified in microsomal membrane preparations prepared from the stomach which is also commonly involved in organ-specific autoimmunity. The 105,000-dalton component does not bind to a Lens culinaris lectin affinity column. We conclude that the epitopes of the microsomal/microvillar antigen are presented on a poorly glycosylated peptide of mol. wt 105,000, which is probably stabilised by intrachain disulphide bonds and which does not share serological reactivity with membrane-bound thyroglobulin.
D000941:Antigens / Q000032:analysis*; D001324:Autoantigens / Q000032:analysis*; D001327:Autoimmune Diseases / Q000276:immunology*; D002846:Chromatography, Affinity; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007425:Intracellular Membranes / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology; D008861:Microsomes / Q000276:immunology; D008871:Microvilli / Q000276:immunology; D008970:Molecular Weight; D009928:Organ Specificity; D011863:Radioimmunoassay; D013954:Thyroglobulin / Q000276:immunology; D013959:Thyroid Diseases / Q000276:immunology*; D013961:Thyroid Gland / Q000276:immunology*
D000941:Antigens; D001324:Autoantigens; D008565:Membrane Proteins; D013954:Thyroglobulin