title: Antibodies cross-reacting with thyroglobulin and thyroid peroxidase are induced by immunization of rabbits with an immunogenic thyroglobulin 20mer peptide.
abstract: Thyroglobulin (Tg) and thyroid peroxidase (TPO) are two major autoantigens in autoimmune thyroid diseases (AITD). Cross-reactive anti-Tg/TPO antibodies have been identified in patients with AITD and in mice immunized with Tg or TPO. In the present study, we investigated the production of anti-Tg/TPO antibodies in rabbits immunized with human Tg and with a highly immunogenic Tg peptide (namely TgP41, sequence 2651-2670 of human Tg), by noncompetitive and competitive ELISA. TgP41 was found previously to induce intramolecular epitope spreading. We found that Tg-immunized rabbits developed a serological immune response to TPO due to cross-reactivity with Tg, since serum TPO reactivity was inhibited by soluble Tg and affinity-purified anti-Tg antibodies cross-reacted with TPO. Moreover, TgP41-immunized rabbits responded to Tg and TPO. This serological response was attributed to anti-Tg/TPO antibodies, based on the observation that serum TPO reactivity was again inhibited by soluble Tg, and affinity-purified anti-Tg antibodies, induced by TgP41-immunization, cross-reacted with TPO. Purified anti-TgP41 antibodies did not react with TPO, suggesting that a putative common antigenic determinant is not included in the peptide sequence. We propose that intermolecular spreading of reactivity to TPO observed after administration of the Tg-peptide is a result of intramolecular epitope spreading to determinant(s) responsible for Tg/TPO cross-reactivity.
authors.affiliation: Laboratory of Immunology, Department of Biochemistry, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Thrasyvoulides
authors.forename: P
authors.initials: P
authors.lastname: Lymberi
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000939:Epitopes / Q000276:immunology; D007114:Immunization / Q000379:methods; D007453:Iodide Peroxidase / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology; D012995:Solubility; D013954:Thyroglobulin / Q000276:immunology*
chemical_list: D000906:Antibodies; D000939:Epitopes; D010446:Peptide Fragments; D011994:Recombinant Proteins; C495286:thyroglobulin peptide (2651-2670); D013954:Thyroglobulin; D007453:Iodide Peroxidase