Discordant Expression of Ii and HLA-DR in Thyrocytes: A Possible Pathogenetic Factor in Hashimoto's Thyroiditis

Abstract

Hashimoto's thyroiditis is the archetype of organ-specific autoimmune disease. The key pathogenetic feature is the activation of thyroid-specific T-cells by properly presented endogenous thyroid antigens. There is strong indication that thyrocytes themselves present self-antigens, based on the finding of antigen presenting human leukocyte antigen-DR (HLA-DR) molecules on the thyrocytes in Hashimoto's thyroiditis. Because class ll-associated invariant chain (Ii) is tightly bound to the antigen-binding groove of the DR molecules in the endoplasmic reticulum and is found to compete with the endogenous peptides for binding with DR. it is speculated that Ii prevents endogenous peptides from binding to, and being presented by, DR on the cell surface. We hypothesize that in Hashimoto's thyroiditis, Ii is insufficient, leaving DR molecules open for endogenous peptides, In this article, we test our hypothesis of discordance between DR and Ii in the thyroid epithelial cells in Hashimoto's thyroiditis by immunohistochemistry. Formalin-fixed, paraffin-embedded archival tissue from eight cases of Hashimoto's thyroiditis and four cases of normal thyroid specimen were randomly selected and immunostained with monoclonal antibodies (MAbs) against HLA-DR and Ii using avidin-biotin-peroxidase method. We found that in all eight cases of Hashimoto's thyroiditis. Ii is significantly reduced relative to DR. The results support our hypothesis that presentation of self-antigen may be a result of insufficient Ii in the thyrocytes in Hashimoto's thyroiditis.