Transcriptional regulation of the MHC II gene DRA in untransformed human thyrocytes

MHC class II molecules are heterodimeric, polymorphic transmembrane glycopr oteins physiologically expressed on cells of the immune system and patholog ically expressed on the affected target cells of autoimmunity. Their functi on is to present processed peptides to antigen-specific CD4(+) T cells. To understand the molecular mechanism of the regulation of class II genes in a utoimmune target cell thyrocytes, we investigated the transcriptional regul ation of DRA on untransformed, differentiated human thyroid cells following IFN-gamma stimulation, which is potentially relevant to the inappropriate class II expression found in Graves' disease. Data from this study show tha t IFN-gamma enhances a promoter Y box binding protein and induces an X box binding protein in untransformed thyrocytes, but not in SV-40-transfected t hyrocytes. Initial characterization of the proteins has indicated that the Y box binding protein is similar to 132 kDa in sire while the X box binding protein binds to the X2 region and is similar to 116 kDa, The X box bindin g protein may correspond to poly(ADP-ribose) polymerase, a recently describ ed component of the X2 box binding protein, X2BP. In addition, the signal t ransducer and activator of transcription 1 alpha protein (STAT1 alpha) is a lso induced by IFN-gamma in these cells. These results further suggest that there are differences in class II gene regulation between differentiated c ells and transformed cell lines.