ANTIGEN PROCESSING GENES AND CELL BIOLOGY

描述（改编自研究者摘要）：长期 该项目的目标是利用遗传和其他方法， 鉴定与HLA II类限制性相关的新基因和基因产物 抗原加工，并确定这些基因产物如何发挥作用。 的 本申请的具体目的是：通过互补确定 分析是否有三种新的抗原加工突变体，其中两种具有 被证明不是DM突变体，受相同或不同的影响， 基因;克隆这些新的抗原处理突变体中受影响的基因 以及在另外的受新抗原加工影响的突变体中 基因;进一步表征三种新抗原中的缺陷 加工突变体，通过连续转录，瞬时表达 DM-报告基因构建体、凝胶迁移分析、DM mRNA稳定性，以及当DM-报告基因构建体 通过DNA和蛋白质序列分析确定受影响的基因， 结构域和基序提供关于功能的信息，通过表达 受影响基因的蛋白质产物，以及抗体的产生 鉴定的基因的产物;以表征缺陷， 定义新基因的其他抗原加工突变体中受影响的基因; 并研究DM功能的某些方面，包括HLA的特征 在抗原中独立于DM发挥功能的等位基因和同种型 表达，以及DM和 使用突变的DM和DR基因转染到DM中的II类分子， DR突变体。 研究人员认为，这些研究将导致 II类中涉及的新基因和基因产物的鉴定 限制抗原加工和了解它们的功能。 抗原加工在宿主抵抗微生物的防御中具有核心作用。 药物，在自身免疫性疾病中可能具有重要意义。 因此这些 基础研究应有助于更好地了解宿主防御 机制，以及增强宿主对微生物的防御的方法， 来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.