CELLULAR & MOLECULAR CONTROL OF IA ANTIGEN EXPRESSION

控制基因表达的细胞和遗传机制 将对小鼠Ia抗原进行研究，以更好地了解 免疫反应的调节。由于Ia抗原表达可以具有 对人类免疫反应的严重程度和类型产生深远的影响 正常和疾病情况下，了解调节机制 Ia在不同细胞类型中的表达是至关重要的。这个 这项建议的具体目的是1)调查细胞内 参与Ia诱导的膜、mRNA和 转录水平。这将涉及不同方法的比较。 Ia的诱导及对蛋白激酶C和蛋白激酶C作用的评价 环磷酸腺苷介导的信号转导通路。2)进一步 描述一种新发现的调节E-β的机制 基因，也就是转录伸长受阻的基因。 干扰素-γ。这将涉及转录的核径流分析。 E-β基因在不同细胞类型中的比率。3)描述 插入到CAT中参与转录阻断的序列 专为评估转录终止而设计的载体 序列。4)评估序列特异性DNA结合的存在 可能与参与转录的区域相互作用的蛋白质 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.