Discordant expression of Ii and HLA-DR in thyrocytes: A possible pathogenetic factor in Hashimoto’s thyroiditis
- 38 Downloads
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 II-associated invariant chain (li) 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 li 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 li 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 li using avidin-biotin-peroxidase method. We found that in all eight cases of Hashimoto’s thyroiditis, li is significantly reduced relative to DR. The results support our hypothesis that presentation of self-antigen may be a result of insufficient li in the thyrocytes in Hashimoto’s thyroiditis.
Key WordsHashimoto’s thyroiditis HLA-DR invariant chain (li) autoimmune disease autoantigen
Unable to display preview. Download preview PDF.
- 3.Rose NR. Autoimmune diseases: tracing the shared threads. Hosp Pract (Off Ed) 32:147–154, 1997.Google Scholar
- 8.Hanafusa T, Pujol-Borrell R, Chiovato L, Russell RC, Doniach D, Bottazzo GF. Aberrant expression of HLA-DR antigen on thyrocytes in Grave’s disease: relevance for autoimmunity. Lancet 2:111–1115, 1983.Google Scholar
- 27.Ericson ML, Sundstrom M, Sansom DM, Charron DJ. Mutually exclusive binding of peptide and invariant chain to major histocompatibility complex class II antigens. J Biol Chem 269:26,531–26,538, 1994.Google Scholar
- 37.Tandon N, Metcalfe RA, Barnett D, Weetman AP. Expression of the constimulatory molecule B7/BB1 in autoimmune thyroid disease. QJ Med 87:231–236, 1994.Google Scholar