ANTIGEN PROCESSING GENES AND CELL BIOLOGY

描述(改编自《调查员摘要》)：长期 该项目的目标是使用遗传和其他方法来 发现与人类白细胞抗原II类受限有关的新基因和基因产物 抗原处理，并确定这些基因产物如何发挥作用。这个 本申请的具体目的是：通过互补性确定 分析三个新的抗原处理突变体，其中两个 被证明不是DM突变体，受到相同或不同的影响 基因；克隆这些新的抗原处理突变体中受影响的基因 以及在新抗原处理过程中受到影响的其他突变体 基因；以进一步表征三种新抗原的缺陷 通过Run-On转录处理突变体，瞬时表达 DM报告基因的构建，凝胶位移分析，DM mRNA的稳定性，以及当 通过DNA和蛋白质序列分析鉴定受影响的基因 关于功能的域和主题，通过表达 受影响基因的蛋白质产物，以及抗体的产生 已识别基因的产物；以表征 定义新基因的其他抗原处理突变体中受影响的基因； 并对DM功能的某些方面进行了研究，包括人类白细胞抗原(HLA)的特性 在抗原上独立于DM发挥作用的等位基因和同型 以及DM和DM相互作用的功能区的映射 利用突变的DM和DR基因导入DM和DR中的II类分子 变种博士。调查人员认为，这些研究将导致 鉴定与第II类有关的新基因和基因产物 限制抗原处理和对其功能的理解。 抗原处理在宿主对微生物的防御中起着核心作用 药物，在自身免疫性疾病中可能具有重要作用。因此，这些 基础研究应有助于更好地理解寄主防御 机制，以及增强宿主对微生物和 以改善自身免疫性疾病。

DESCRIPTION (Adapted from the Investigator's abstract): The long term objectives of this project are to use genetic and other approaches to identify new genes and gene products involved in HLA class II restricted antigen processing, and to determine how these gene products function. The specific aims of this application are: to determine by complementation analysis whether three new antigen processing mutants, two of which have been shown not to be DM mutants, are affected for the same or different genes; to clone the genes affected in these new antigen processing mutants and in additional mutants which are affected for new antigen processing genes; to further characterize the defects in the three new antigen processing mutants, by run-on transcription, transient expression of DM-reporter constructs, gel shift assays, DM mRNA stability and, when the affected genes are identified, by DNA and protein sequence analysis for domains and motifs informative regarding function, by expression of the protein products of the affected genes, and by the generation of antibodies to the products of the identified genes; to characterize the defects in the affected genes in other antigen processing mutants which define new genes; and to study some aspects of DM function, including characterization of HLA alleles and isotypes which function independently of DM in antigen presentation, and the mapping of functional regions of interaction of DM and class II molecules using transfection of mutated DM and DR genes into DM and DR mutants. The investigators believe that these studies will lead to the identification of new genes and gene products involved in class II restricted antigen processing and an understanding of their functions. Antigen processing has a central role in host defenses against microbial agents and is of likely importance in diseases of autoimmunity. Thus these basic studies should lead to a better understanding of host defense mechanisms, and of ways to enhance host defenses against microorganisms and to ameliorate autoimmune diseases.