CELLULAR & MOLECULAR CONTROL OF IA ANTIGEN EXPRESSION

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The cellular and genetic mechanisms that control the expression of the murine Ia antigens will be studied in an effort to better understand the regulation of the immune response. Since Ia antigen expression can have a profound effect on the severity and type of immune response generated in normal and disease situations, understanding the mechanisms of regulation of Ia expression in different cell types is of central importance. The specific aims of this proposal are 1) To investigate the intracellular pathways involved in Ia induction at the membrane, mRNA and transcriptional levels. This will involve comparison of different methods of Ia induction and evaluation of the roles of protein kinase C and cyclic AMP-mediated signal transduction pathways. 2) To further characterize a newly discovered mechanism of regulation of the E-beta gene, namely, a block in transcriptional elongation that is regulated by IFN-gamma. This will involve nuclear run-off analysis of transcription rates along the E-beta gene in different cell types. 3) Characterize the sequence involved in the transcriptional blockage by insertion into CAT vectors specifically designed to evaluate transcriptional termination sequences. 4) Evaluate the presence of sequence specific DNA binding proteins that may interact with the region involved in transcriptional blockage.