GENETIC CONTROL OF THE IMMUNE RESPONSE

免疫反应的基因控制

• 批准号: 3085202
• 负责人: Thomas Croghan
• 金额: $ 6.54万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3085202
• 关键词: alleles; chemical structure function; genetic manipulation; genetically modified animals; histocompatibility antigens; laboratory mouse; major histocompatibility complex; point mutation

There is abundant evidence to suggest that the MHC Class II molecules (Ia antigens) are critically involved in the regulation of the immune response. Previous biochemical and molecular analysis has led to great insight into the functional characteristics of these molecules. The current proposal is designed to further this knowledge by analysis of the individual allelic hypervariable regions of the I-A beta chain. Initial experiments will result in the creation of transgenic mice expressing the Ab beta chain (a responder phenotype for the polypeptide antigen (T, G)-A--L) on the normally non-responder H-2s background. Should the presence of the Ab gene product result in the production of an immune response when these mice are stimulated with (T,G)-A--L, I will produce additional transgenic mouse strains, each expressing site- directed I-A beta chain mutants, in which one or more of the allelic hypervariable regions from the responder beta chain allele have been transferred into a non-responder sequence. Such transgenic mice will then be tested for immune responsiveness and expression of alloantigenic determinants, and the series of mutants can systematically test structure-function relationships.

有大量证据表明 MHC II 类 分子（Ia 抗原）关键参与调节 免疫反应。 以前的生化和分子 分析使人们对功能特性有了深入的了解 这些分子。 目前的提案旨在进一步 通过分析个体等位基因高变量获得这一知识 I-A β 链区域。 初步实验将导致 表达 Ab β 链的转基因小鼠的创建（a 多肽抗原 (T, G)-A--L) 的反应者表型 通常无应答的 H-2s 背景。 如果存在 Ab基因产物的结果导致产生免疫 当这些小鼠受到 (T,G)-A--L 刺激时的反应，我会 产生额外的转基因小鼠品系，每个表达位点- 定向 I-A β 链突变体，其中一个或多个 来自反应者β链等位基因的等位基因高变区 已转入无应答序列。 这样的 然后将测试转基因小鼠的免疫反应性 和同种异体抗原决定簇的表达，以及一系列 突变体可以系统地测试结构-功能关系。