CELLULAR & MOLECULAR CONTROL OF IA ANTIGEN EXPRESSION

蜂窝网络

• 批准号: 3177832
• 负责人: Jerold G Woodward
• 金额: $ 11.84万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1991-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3177832
• 关键词: DNA binding protein; biological signal transduction; cell membrane; cell population study; cell type; cyclic AMP; flow cytometry; gene expression; genetic manipulation; genetic transcription; histocompatibility antigens; immunogenetics; immunoregulation; interferons; laboratory mouse; major histocompatibility complex; messenger RNA; nucleic acid sequence; phosphatidylinositols; protein kinase C; transposon /insertion element

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.

控制表达的细胞和遗传机制 将研究鼠 Ia 抗原，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，了解调节机制 Ia 在不同细胞类型中的表达至关重要。这 该提案的具体目标是 1) 研究细胞内 参与膜 Ia 诱导、mRNA 和 转录水平。这将涉及不同方法的比较 Ia 的诱导和蛋白激酶 C 的作用评估 环AMP介导的信号转导途径。 2）进一步 表征新发现的 E-beta 调节机制 基因，即转录延伸的一个区块，受以下因素调节 干扰素-γ。这将涉及转录的核径流分析 不同细胞类型中 E-beta 基因的速率。 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。 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。