Enhancing or suppressive effects of antibodies on processing of a pathogenic T cell epitope in thyroglobulin

Thyroglobulin (Tg)-specific Abs occur commonly in thyroid disease, but it i s not clear to what extent they affect Tg processing and presentation to T cells. Here we show that generation of the nondominant pathogenic Tg epitop e (2549-2560), containing thyroxine (T4) at position 2553 (T4(2553)), is au gmented by Tg-specific IgG mAbs that facilitate FcR-mediated internalizatio n of Tg. However, other mAbs of the same (IgG1) subclass enhanced Tg uptake by APC but had no effect on the generation of this peptide. Treatment of A PC with chloroquine or glutaraldehyde abrogated enhanced generation of T4(2 553), The boosting effect was selective, since the enhancing mAbs did not f acilitate generation of the neighboring cryptic (2495-2511) peptide, which is also pathogenic in mice. When Tg was simultaneously complexed to a mAb r eactive with T4(2553) and to a mixture of boosting mAbs, the presentation o f this epitope was totally suppressed. These results suggest that Tg-specif ic Abs alter Tg processing and may boost or suppress the presentation of no ndominant pathogenic determinants during the course of disease.