ORGANIZATION AND FUNCTIONS OF THE H-2 GENE COMPLEX

H-2 基因复合体的组织和功能

• 批准号: 3480700
• 负责人: DONALD C. SHREFFLER
• 金额: $ 38.89万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-01-01 至 1990-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3480700
• 关键词: B lymphocyte; T lymphocyte; chemical cleavage; complement pathway; gene expression; genetic mapping; genetic recombination; genetic regulation; glycosylation; histocompatibility gene; hormone regulation /control mechanism; immunoregulation; laboratory mouse; macrophage; major histocompatibility complex; mixed tissue /cell culture; monoclonal antibody; mutant; proteolysis

The murine H-2 major histocompatibility complex or MHC controls a diverse set of products and traits whose definition is important to the understanding of fundamental genetic and immunologic mechanisms, as well as to clinically relevant research in transplantation and disease resistance. In the latter context, H-2 is an important experimental model for the human MHC, the HLA gene complex, because of their remarkable genetic and functional homology. The long-term objective of this research is to resolve, by genetic, biochemical and functional approaches, the multiple genes of the H-2 complex, in order to advance our understanding of the organization, evolution and regulation of the MHC genes. This research will focus particularly upon the genes of the internal I and S regions of the H-2 complex, whose products mediate macrophage-T lymphocyte-B lymphocyte regulatory interactions, and reactions of the complement pathways, respectively. Two general approaches are to be taken: 1) Efforts will be made to detect and characterize new mutations and recombinations, to improve H-2 genetic fine structure mapping and to provide new and useful stocks for further functional and biochemical studies. Progeny from mutagen-treated parents will be screened by mixed leucocyte reactions and with monoclonal antibodies to cellular alloantigens. Variants will be characterized serologically, biochemically and functionally, with emphasis on improved definition of the I-A, I-B, I-J, S and D regions. 2) The structure, synthesis and processing of the S region C4 and Slp protein will be investigated, to better define the genetic information that specifies their structures and the genetic and hormonal regulatory mechanisms that control their expression. Peptide mapping and amino acid sequence determinations will be done. The roles of proteolytic cleavage and of glycosylation in processing of intracellular precursors will be examined. Tissue sites of synthesis will be determined. C4 and Slp mRNA will be examined to probe regulatory mechanisms. Non-H-2 genes regulating Slp expression will be further defined.

小鼠H-2主要组织相容性复合体或MHC控制着一系列不同的 产品和特征的定义对理解 基本的遗传和免疫学机制以及临床上 移植和抗病方面的相关研究。在后者中 背景，H-2是人类MHC--人类白细胞抗原基因的重要实验模型 复杂，因为它们在基因和功能上具有显著的同源性。这个 这项研究的长期目标是通过遗传、生化和 功能途径，即H-2复合体的多个基因，以便 增进我们对组织、演变和监管的理解 MHC基因。这项研究将特别集中在内部的基因 H-2复合体的I和S区，其产物介导巨噬细胞-T 淋巴细胞-B淋巴细胞的调节相互作用和补体反应 分别是路径。一般采取两种方法：1)努力 将被用于检测和表征新的突变和重组，以 改进H-2基因精细结构作图，提供新的有用种质 用于进一步的功能和生化研究。诱变剂处理的后代 父母将通过混合白细胞反应和单克隆性筛选 针对细胞同种异体抗原的抗体。变种将被描述为 从血清学、生化和功能上讲，重点是改善 I-A、I-B、I-J、S和D区的定义。2)结构、合成 并对S C4区和SLP蛋白的加工进行了研究 更好地定义指定其结构的遗传信息和 控制其表达的基因和激素调节机制。 将进行多肽图谱和氨基酸序列测定。角色 胞内加工中的蛋白水解性切割和糖基化 将对前兆进行审查。合成的组织部位将被确定。C4 并将检测SLP基因的表达，以探讨其调控机制。非H-2基因 对SLP表达的调控将进一步明确。