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International Immunology, Vol. 12, No. 4, 405-413, April 2000
© 2000 Japanese Society for Immunology

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

Zhonglin Wu3, Paul Andrew Biro, Rita Mirakian, Francesco Curcio1, Francesco Saverio Ambesi-Impiombato1 and Gian Franco Bottazzo2

Department of Immunology, St Bartholomew's and the Royal London School of Medicine and Dentistry, London EC1A 7BE, UK
1 Dipartimento di Patologia e Medicina Sperimentale e Clinica, Università degli Studi di Udine, 33100 Udine, Italy
2 Direzione Scientifica, Ospedale Pediatrico Bambino Gesù, Scientific Institute, Piazza S. Onofrio 4, 00165 Rome, Italy

Correspondence to: G. F. Bottazzo

MHC class II molecules are heterodimeric, polymorphic transmembrane glycoproteins physiologically expressed on cells of the immune system and pathologically expressed on the affected target cells of autoimmunity. Their function is to present processed peptides to antigen-specific CD4+ T cells. To understand the molecular mechanism of the regulation of class II genes in autoimmune target cell thyrocytes, we investigated the transcriptional regulation 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 that 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 thyrocytes. Initial characterization of the proteins has indicated that the Y box binding protein is ~132 kDa in size while the X box binding protein binds to the X2 region and is ~116 kDa. The X box binding protein may correspond to poly(ADP-ribose) polymerase, a recently described component of the X2 box binding protein, X2BP. In addition, the signal transducer and activator of transcription 1{alpha} protein (STAT1{alpha}) is also induced by IFN-{gamma} in these cells. These results further suggest that there are differences in class II gene regulation between differentiated cells and transformed cell lines.

Keywords: MHC class II, thyrocytes, transcriptional regulation

3 Present address: Division of Renal Medicine, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK

Transmitting editor: G. Doria


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