ANTIGEN PROCESSING GENES AND CELL BIOLOGY

描述：(改编自申请人的摘要)总体目标 该项目的主要目的是阐明抗原提呈细胞 处理外源抗原以呈递给T细胞。具体目标 1)鉴定B细胞系突变体的缺陷，这些缺陷 无法将人类白细胞抗原II类限制性抗原呈递给抗原特异性T细胞 细胞；2)克隆与抗原加工有关的基因；3)研究 抗原突变效应的“占有性”假说 处理基因对人类白细胞抗原II类分子构象的影响；以及4) 研究联合免疫缺陷患者的抗原处理缺陷。 克隆抗原处理基因的基本策略将是 将各种克隆的基因和基因库导入 抗原处理突变体，并筛选其缺陷已被 辅以引入的DNA。免疫显微镜和生化 将使用方法来表征抗原处理过程中的缺陷。 变种人。“占有率”假说将通过以下约束性研究进行检验 从抗原处理突变体中将多肽转化为II类分子。细胞系 来自不明原因的联合免疫缺陷患者 分析抗原处理过程中的缺陷。预计 这些突变体的基本缺陷的详细特征以及 克隆它们的突变基因的正常同源基因，如这里所建议的， 将提供有关抗原处理的重要信息，关于II类 生物合成和表达，以及同种异体识别的性质。

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.