GENETIC REGULATION OF LYMPHOID DIFFERENTIATION ANTIGENS

本项目的总体目标是通过以下方式阐明这些机制： 哪些HLA II类基因受到调节。 具体目标是 项目周期是：1）继续和完成开发的方法， 克隆反式转录因子，逆转录病毒反式激活， 其不基于蛋白质-DNA结合，也不依赖于mRNA 丰度; 2）鉴定和克隆转录因子的基因， 特别是非DNA结合转录因子，其调节 HLA II类基因和其他在免疫中重要的基因的表达 3）研究HLA II类基因的转录调控 使用克隆的反式因子基因;和4）继续 影响HLA-II翻译后机制研究 基因表达和功能。 将使用两种一般方法， 克隆II类转录因子，逆转录病毒反式激活和 II类反式因子突变体的互补。 我们预计 使用克隆的反式调节基因的研究将导致更好的 了解II类基因的调控方式。因为 T细胞反应的大小取决于II类 抗原呈递细胞的表达，这些研究反过来应该有助于 阐明T细胞功能的重要决定因素。 此外我们 希望能阐明基因正常功能的本质 突变成各种形式的裸淋巴细胞综合征

The overall objective of this project is to elucidate the mechanisms by which HLA class II genes are regulated. The specific aims for this project period are: 1) to continue and complete development of a method of cloning transactive transcriptional factors, retroviral transactivation, which is not based on protein-DNA binding and is not dependent on mRNA abundance; 2) to identify and clone genes for transcription factors, particularly non-DNA binding transcription factors, which regulate expression of HLA class II genes and other genes important in the immune response; 3) to study transcriptional regulation of HLA class II genes using the cloned transactive factor genes; and 4) to continue investigation of post-translational mechanisms which effect HLA class II gene expression and function. Two general approaches will be used for cloning class II transcriptional factors, retroviral transactivation and complementation of class II transactive factor mutants. We expect that studies using cloned transactive regulatory genes will lead to a better understanding of the way that class II genes are regulated. Because the magnitude of T cell responses is dependent on levels of class II expression of antigen presenting cells, these studies in turn should help to elucidate an important determinant of T cell function. In addition we hope to elucidate the nature of the normal functioning of the genes mutated in the various forms of the Bare Lymphocyte Syndrome.