Modifying effects of iodine on the immunogenicity of thyroglobulin peptides

We have previously shown that iodotyrosyl formation within thyroglobulin (Tg) generates neoantigenic determinants that are immunopathogenic. In the current study, we have examined iodination effects on three tyrosyl-containing Tg peptides that are immunogenic in their non-iodinated form. We found that iodotyrosyl formation can enhance (p179, a.a. 179-194), suppress (p2540, a.a. 2540-2554), or not alter (p2529, a.a. 2529-2545) the immunogenic profiles of these peptides at the T-cell level. On the other hand, iodination did not alter the MHC-restriction profile of p2529 and p2540 (A(k)-binders) or p179 (A(k)- and E(k)-binder) and did not significantly influence the pathogenicity of these determinants. At the B-cell level, addition of an iodine atom on Y192 in p179 generated a neoantigenic determinant, but analogous effects were not discernible in p2529 or p2540. Our results demonstrate that iodotyrosyl formation can exert variable effects on the immunogenic behavior of Tg epitopes which may not always result in enhanced pathology. These findings also suggest that variations in the iodine content of Tg may significantly alter the hierarchy of antigenic determinants, to which the immune system may or may not be tolerant.