CELLULAR & MOLECULAR CONTROL OF IA ANTIGEN EXPRESSION

细胞和遗传机制控制的表达， 将对鼠Ia抗原进行研究，以更好地了解 调节免疫反应。由于Ia抗原表达可具有 对免疫反应的严重程度和类型产生深远的影响， 正常和疾病的情况下，了解调节机制 Ia在不同细胞类型中的表达是至关重要的。的 该建议的具体目的是1）研究细胞内 参与Ia诱导的途径在膜，mRNA和 转录水平。这将涉及不同方法的比较 Ia诱导和蛋白激酶C的作用的评估， 环腺苷酸介导的信号转导途径。2)进一步 描述了一种新发现的调节E-β的机制， 基因，即转录延伸的阻断，其由 IFN-γ。这将涉及转录的核径流分析 对不同细胞类型中的E-β基因进行沿着评级。3)表征 通过插入CAT参与转录阻断的序列 专门设计用于评估转录终止的载体 序列的4)评价是否存在序列特异性DNA结合 可能与转录调控区相互作用的蛋白质 堵塞。

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.