Hyperexpression of transporter in antigen processing-1 (TAP-1) in thyroid glands affected by autoimmunity: a contributory factor to the breach of tolerance to thyroid antigens?

Abstract

SUMMARYAccording to the 'aberrant HLA expression' hypothesis, endocrine autoimmunity is driven by presentation of self antigens by target cells over-expressing HLA molecules. In autoimmune thyroid diseases (AITD), thyroid follicular cells (thyrocytes) over-express HLA class I and HLA class II molecules. Since efficient presentation of endogenous peptides via class I requires transporters that translocate endogenous peptides from the cytoplasm to the endoplasmic reticulum, i.e. transporters associated with antigen processing (TAP) -1 and -2, the capability of thyrocytes to express TAP and whether TAP is hyperexpressed in AITD glands are issues relevant to the above hypothesis. Results from immunofluorescence and Northern blotting studies on primary thyrocyte cultures and on a thyroid cell line demonstrate that thyrocytes express constitutively TAP-1 at a low level, and that this expression is readily induced by interferon-gamma (IFN-g) and to a lesser extent by IFN-a. In AITD, but not in non-autoimmune glands, thyrocytes hyperexpress TAP-1, as demonstrated by both immunohistopathology and flow cytometry. The cytokine pattern does not bear, as assessed by reverse transcriptase-polymerase chain reaction (RT-PCR), a clear relationship with TAP-1 expression. These results have broad implications and suggest that the core concept of the 'aberrant HLA expression' hypothesis of endocrine autoimmunity could be incorporated in the currently prevailing view of 'autoimmunity by breach of peripheral tolerance'.

Single‐cell analysis of intrathyroidal lymphocytes shows differential cytokine expression in Hashimoto's and Graves' disease

“…Since all of these clones were low IL-2 producers and did not proliferate efficiently in response to autologous TFC, it was assumed that cells responding to both TPO and TSH-R are Th2-like. This contrasts with published data suggesting the association of TPO and TSH-R with Thl and Th2 responses, respectively [33].…”

Proteasome subunits, low‐molecular‐mass polypeptides 2 and 7 are hyperexpressed by target cells in autoimmune thyroid disease but not in insulin‐dependent diabetes mellitus: implications for autoimmunity

“…It has been known for over ten years that thyrocytes in AITD hyperexpress HLA class I and HLA class I1 molecules (7,40). We have recently found in the same cells augmented TAP-1 expression (28,29). We demonstrate here that another two HLA region encoded proteins, LMP2 and LMP7, are hyperexpressed in thyrocytes of AITD gland.…”

HLA-DMB expression by thyrocytes: indication of the antigen-processing and possible presenting capability of thyroid cells

“…Professional APC such as dendritic cells also play a vital role in presenting thyroid autoantigens and providing costimulatory molecules in AITD. Similar to HLA class I and transporter associated with antigen processing (TAP)-1 expression, the hyperinducibility of class II genes in thyrocytes from GD has been thought to be due to a breach of peripheral tolerance [41,42]. However, with the theoretical models of Matzinger, this concept has to be reviewed and it would be critical to understand what the costimulatory signals are and how dendritic cells, lymphocytes and thyrocytes interact in AITD as a whole [43][44][45].…”