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

According to the 'aberrant HLA expression' hypothesis, endocrine autoi mmunity is driven by presentation of self antigens by target cells ove r-expressing HLA molecules. In autoimmune thyroid diseases (AITD). thy roid follicular cells (thyrocytes) over-express HLA class I and HLA cl ass 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 as sociated with antigen processing (TAP) -1 and -2, the capability of th yrocytes to express TAP and whether TAP is hyperexpressed in AITD glan ds are issues relevant to the above hypothesis. Results from immunoflu orescence and Northern blotting studies on primary thyrocyte cultures and on a thyroid cell line demonstrate that thyrocytes express constit utively TAP-1 at a low level, and that this expression is readily indu ced by interferon-gamma (IFN-gamma) and to a lesser extent by IFN-alph 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 transcrip tase-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 endocr ine autoimmunity could be incorporated in the currently prevailing vie w of 'autoimmunity by breach of peripheral tolerance'.