title: The thyroxine-containing thyroglobulin peptide (aa 2549-2560) is a target epitope in iodide-accelerated spontaneous autoimmune thyroiditis.
abstract: Enhanced iodide ingestion is known to accelerate the incidence and severity of spontaneous autoimmune thyroiditis [iodide-accelerated spontaneous autoimmune thyroiditis (ISAT)] in NOD.H2(h4) mice. CD4+ cells are required for the development and maintenance of ISAT, but their target epitopes remain unknown. In this study, we show that the previously identified thyroglobulin (Tg) T cell epitope p2549-2560 containing thyroxine at position 2553 (T4p2553) induces thyroiditis as well as strong specific T and B cell responses in NOD.H2(h4) mice. In ISAT, activated CD4+ T cells specific for T4p2553 are detected before the disease onset in thyroid-draining cervical lymph nodes only in mice placed on an iodide-rich diet and not in age-matched controls. In addition, selective enrichment of CD4+ IFN-γ+ T4p2553-specific cells is observed among cervical lymph node cells and intrathyroidal lymphocytes. T4p2553 was equally detectable on dendritic cells obtained ex vivo from cervical lymph node cells of NaI-fed or control mice, suggesting that the iodide-rich diet contributes to the activation of autoreactive cells rather than the generation of the autoantigenic epitope. Furthermore, spontaneous T4p2553-specific IgG are not detectable within the strong Tg-specific autoantibody response. To our knowledge, these data identify for the first time a Tg T cell epitope as a spontaneous target in ISAT.
authors.affiliation: Division of Endocrinology, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador A1B 3V6, Canada Division of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador A1B 3V6, Canada;
authors.forename: Panayota
authors.initials: P
authors.lastname: Kolypetri
authors.affiliation: Division of Endocrinology, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador A1B 3V6, Canada Division of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador A1B 3V6, Canada;
authors.forename: Karen
authors.initials: K
authors.lastname: Carayanniotis
authors.affiliation: Department of Chemistry, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador A1B 3X7, Canada; and.
authors.forename: Shofiur
authors.initials: S
authors.lastname: Rahman
authors.affiliation: Department of Chemistry, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador A1B 3X7, Canada; and.
authors.forename: Paris E
authors.initials: PE
authors.lastname: Georghiou
authors.affiliation: Department of Pharmacy, University of Patras, Patras 25604, Greece.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Magafa
authors.affiliation: Department of Pharmacy, University of Patras, Patras 25604, Greece.
authors.forename: Paul
authors.initials: P
authors.lastname: Cordopatis
authors.affiliation: Division of Endocrinology, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador A1B 3V6, Canada Division of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador A1B 3V6, Canada; gcarayan@mun.ca.
authors.forename: George
authors.initials: G
authors.lastname: Carayanniotis
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D012974:Sodium Iodide / Q000633:toxicity*; D013954:Thyroglobulin / Q000235:genetics / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology
chemical_list: D001323:Autoantibodies; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D010455:Peptides; D007371:Interferon-gamma; D013954:Thyroglobulin; D012974:Sodium Iodide