ANTIGEN PROCESSING GENES AND CELL BIOLOGY

抗原加工基因和细胞生物学

• 批准号: 3145534
• 负责人: DONALD A PIOUS
• 金额: $ 19.12万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-01 至 1995-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3145534
• 关键词: MHC class II antigen; T lymphocyte; antigen presentation; antigen presenting cell; chemical binding; gene expression; genetic library; genetic manipulation; human tissue; molecular cloning; mutant; tissue /cell culture; transfection

DESCRIPTION: (Adapted from the applicant's abstract) The overall objective of this project is to elucidate pathways by which antigen presenting cells process exogenous antigens for presentation to T cells. The specific aims are: 1) to characterize the defects in B cell line mutants which are unable to present HLA class II restricted antigens to antigen specific T cells; 2) to clone genes involved in antigen processing; 3) to investigate the "occupancy" hypothesis for the effect of mutations in antigen processing genes on the conformation of HLA class II molecules; and 4) to study combined immunodeficiency patients for defects in antigen processing. The basic strategy for cloning antigen processing genes will be to transfect various cloned genes and gene libraries into the antigen-processing mutants and to select for mutants whose defect has been complemented by the introduced DNA. Immunomicroscopic and biochemical approaches will be used to characterize the defects in antigen processing mutants. The "occupancy" hypothesis will be tested by binding studies of peptides to class II molecules from antigen processing mutants. Cell lines from patients with combined immunodeficiency of unknown etiology will be analyzed for defects in antigen processing. It is anticipated that detailed characterization of the basic defects in these mutants and the cloning of the normal homologues of their mutant genes, as proposed here, will yield important information on antigen processing, on class II biosynthesis and expression, and on the nature of allorecognition.

描述：（改编自申请人的摘要）总体目标 这个项目的目的是阐明抗原呈递细胞 处理外源抗原以呈递给T细胞。 具体目标 是：1）表征B细胞系突变体中的缺陷， 不能将HLA II类限制性抗原呈递给抗原特异性T细胞 细胞; 2）克隆参与抗原加工的基因; 3）研究 抗原突变效应的“占据”假说 根据HLA II类分子的构象处理基因;以及4） 研究联合免疫缺陷患者的抗原加工缺陷。 克隆抗原加工基因的基本策略是： 将各种克隆基因和基因文库导入 抗原加工突变体，并选择其缺陷已 由引入的DNA补充。 免疫显微镜和生化 方法将用于表征抗原加工中的缺陷 变种人 “占有”假设将通过以下结合研究进行检验： 从抗原加工突变体的肽到II类分子。 细胞系 来自病因不明的联合免疫缺陷患者的 分析抗原处理中的缺陷。 预计各国 这些突变体中基本缺陷的详细表征以及 克隆其突变基因的正常同源物，如本文所提出的， 将产生关于抗原加工的重要信息， 生物合成和表达，以及异源识别的性质。