Thyroglobulin Peptides of Specific Primary Hormonogenic Sites Can Generate Cytotoxic T Cells and Serve as Target Autoantigens in Experimental Autoimmune Thyroiditis

Abstract

Previously we demonstrated that thyroxine (T4)-containing, 12-mer peptides from positions 5 (1–12) and 2553 (2549–2560), as well as thyronine (T0)-substituted 2553 peptide, derived from human (H) thyroglobulin (Tg) are capable of activating T cells that infiltrate the thyroid (thyroiditogenic). In contrast, peptides T4(2567) and T0(2567) (2559–2570) are not. To determine if these thyroiditogenic peptides, T4(5), T4(2553), and T0(2553), activated cytotoxic T cells (Tc) and served as target autoantigens when loaded onto indicator cells (BW5147 lymphoma,H2k), lymph node cells from CBA mice immunized with mouse (M) Tg were culturedin vitrowith MTg, HTg, or Tg peptide. After MTg or HTg activation, Tc were detected for both MTg- and HTg-loaded target cells in an 18-h,51Cr-release assay at an effector:target cell ratio of 50:1. These Tc also killed target cells labeled with T4(5), T4(2553), or T0(2553), but not the control peptide T4(2567). When MTg-primed lymphocytes were cultured with T4(5), T4(2553), or T0(2553), specific Tc were also generated against target cells labeled with the respective peptide. The data suggest that one of the thyroiditogenic properties of these peptides previously shown by adoptive transfer of thyroiditis is related to the generation of Tc. In addition, these conserved autoepitopes of Tg also serve as target antigens for Tc.