PRIMARY HORMONOGENIC SITES AS CONSERVED AUTOEPITOPES ON THYROGLOBULININ MURINE AUTOIMMUNE-THYROIDITIS - SECONDARY ROLE OF IODINATION

We hypothesized earlier that conserved T cell epitopes and those uniqu e to mouse thyroglobulin (MTg) contributed to its total thyroiditogeni city in murine autoimmune thyroiditis. Recent studies of synthetic pep tides from human Tg (HTg) revealed no immunodominant epitopes. The rol e of iodine residues, considered by some to render Tg immunogenic, bec ame unclear, since only one 12-mer peptide contained thyroxine (T4) po sitioned at hormonogenic site 2553. It primed T cells for thyroiditis transfer, but noniodinated peptide containing thyronine (TO) was not c ompared. To determine 1) whether other primary hormonogenic sites were likewise immunogenic and 2) whether iodination was requisite for this and other sites to be an autoepitope, we derivatized three pairs of 1 2-mer peptides, 1-12, 2549-2570, 2559-2570, containing TO or T4 at pos itions 5, 2553, or 2567, respectively. The six peptides were used to s timulate MTg-primed cells in vitro and to immunize mice, None directly induced thyroiditis; peptide Abs were the lowest in mice given hT0(25 67) or hT4(2567). Of the three T4-containing peptides, hT4(5) and hT4( 2553), but not hT4(2567), stimulated MTg-primed or HTg-primed T cells in vitro, with hT4(2553) being the stronger. Comparing hT0(2553) with hT4(2553), both activated MTg-primed, or peptide-primed, T cells to tr ansfer thyroiditis. The marked immunogenicity of noniodinated hT0(2553 ) and the poor antigenicity of hT4(5) and hT4(2567) demonstrate that i mmunogenicity of a conserved hormonogenic site is dependent more on it s amino acid sequence than on T4 substitution. Iodination may enhance antigenicity and/or binding affinity, but it is not required for a Tg hormonogenic site to be an autoepitope.