The Class II major histocompatibility antigens play a central role in the development of an immune response. These molecules interact with antigen and are recognized by T helper cells in a very specific manner. They are expressed on a variety of cells but most notably B lymphocytes and macrophages. The B lymphocytes constitutively express Class II molecules, while macrophages normally do not synthesize, but can be induced to express them by treating the cells with interferon-gamma. The projects described in this proposal are aimed at understanding the cell specific and interferon-gamma regulated expression of Class II genes. The first specific aim is to identify cis acting DNA sequences within flanking the I-A beta gene which are responsible for the regulated expression of I-A beta. One of the primary goals is to identify the cis acting upstream regulatory elements which are responsible for the regulation of I-A beta gene expression by interferon-gamma. Another goal is to identify the enhancer associated with the I-A beta gene. The second specific aim is to identify and characterize transcription factors which are necessary for I-A beta gene expression. Those factors which are responsible for the cell type specificity of expression or modulate I-A beta gene expression in response to interferon-gamma treatment will be searched for. These transcription factors will be characterized in an in vitro transcription assay. Partial purification of these factors should help to identify their importance in the transcription of MHC class II genes. To complement the work using in vitro transcription we also propose to select mutants that are deficient in class II gene transcription for further characterization.
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