MOLECULAR GENETIC ANALYSIS OF LYMPHOCYTE FUNCTION

淋巴细胞功能的分子遗传学分析

• 批准号: 3818217
• 负责人: D H MARGULIES
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3818217
• 关键词: T lymphocyte; chemical structure function; gene expression; genetic manipulation; genetically modified animals; histocompatibility antigens; human subject; immunoregulation; laboratory mouse; leukocyte activation /transformation; major histocompatibility complex; membrane activity; membrane proteins; molecular cloning; molecular genetics; protein engineering; protein sequence; receptor; tissue /cell culture

The ongoing focus of the laboratory is to understand in detail the structure/function relationships of cell surface molecules involved in the immune response. In particular, we have made significant progress over the past year in several areas: A. generating a panel o molecularly engineered soluble counterparts of the murine class I major histocompatibility antigens H-2Kb, H-2Dd, H-2Ld, H- 2Kk, H-2Kbm6, H-2Kbm8, H-2Kbm10, and the human class I MHC molecule HLA-A2; B. using these soluble molecules to study he biochemical requirements for activation of allospecific T lymphocytes; C. using these soluble molecules to estimate the affinity of an H-2Kb- reactive T cell receptor for the H-2Kb molecule; D. identifying a region of the class I molecule that appears to be a major T cell receptor binding site; E. studying he binding of antigenic viral peptides to purified soluble MHC class I molecules; F. producing transgenic mice that express a soluble counterpart of the soluble H-2Dd molecule to study fundamental questions of the generation of T cell tolerance and education; G. developing a strategy for the production of soluble counterparts of membrane molecules allowing dimeric production and simple purification.

实验室的持续重点是详细了解 涉及的细胞表面分子的结构/功能关系 在免疫反应中。 特别是，我们做出了重大的 在过去的一年里，在几个领域取得了进展：A。生成 图0小鼠的分子工程可溶性对应物 I类主要组织相容性抗原H-2Kb、H-2Dd、H-2Ld、H- 2Kk、H-2Kbm 6、H-2Kbm 8、H-2Kbm 10和人I类MHC分子 HLA-A2; B.利用这些可溶性分子来研究生物化学 同种异体特异性T淋巴细胞活化的要求; C.使用 这些可溶性分子来估计H-2Kb- H-2Kb分子的反应性T细胞受体;识别 I类分子的区域，似乎是主要的T细胞 受体结合位点; E.研究抗原性病毒的结合 肽与纯化的可溶性MHC I类分子的结合; F.生产 转基因小鼠表达可溶性的可溶性对应物， H-2Dd分子来研究生成 T细胞耐受与教育;制定战略， 产生膜分子的可溶性对应物， 二聚体的生产和简单的纯化。