Autoreactive IgG elicited in mice by the non-dominant but pathogenic thyroglobulin peptide (2495-2511): implications for thyroid autoimmunity.
We have previously shown that mice challenged with the rat thyroglobulin (Tg) peptide TgP1 (corresponding to aa 2495-2511 of human Tg) develop experimental autoimmune thyroiditis (EAT) and produce IgG antibodies that cross-react with Tg from various species. It was not clear, however, whether such antibodies were TgP1-specific or were induced secondarily--i.e. by autologous Tg released from the destroyed gland--and therefore directed to determinants other than TgP1. In this study we describe that, 5 weeks after priming with TgP1, the binding of serum IgG on native Tg is completely inhibited by free peptide, suggesting lack of recognition of other determinants on mouse Tg (mTg). In addition, TgP1-induced but not mTg-induced IgG bound better to heat-denatured than intact mTg, a result compatible with the recognition of a linear epitope by the peptide-induced antibodies. Comparison of the IgG subclass distribution among mTg-induced versus TgP1-induced IgG did not reveal qualitative differences, since all subclasses were represented in the order IgG1 > IgG2b > IgG2a > IgG3. Finally, TgP1-specific IgG reacted strongly with the follicular colloid in sections of normal thyroids, indicating the potential to bind to native Tg in vivo. These data: (i) highlight TgP1 as the only, so far, Tg sequence known to generate both EAT and Tg-reactive IgG in mice; and (ii) do not provide evidence for an amplification of the Tg-specific IgG response through the involvement of endogenous autoantigen in EAT.
Chronopoulou
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Division of Endocrinology, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
Michalak
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Carayanniotis
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D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001324:Autoantigens / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005260:Female; D005455:Fluorescent Antibody Technique; D007074:Immunoglobulin G / Q000096:biosynthesis*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D013954:Thyroglobulin / Q000276:immunology*; D013961:Thyroid Gland / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D007074:Immunoglobulin G; D010446:Peptide Fragments; C089808:thyroglobulin peptide (2495-2511); D013954:Thyroglobulin