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: 3480696
• 负责人: DONALD C. SHREFFLER
• 金额: $ 36.15万
• 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/3480696
• 关键词: B lymphocyte; T lymphocyte; chemical cleavage; complement pathway; gene expression; genetic mapping; genetic recombination; genetic regulation; histocompatibility gene; hormone regulation /control mechanism; immunoregulation; 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.

鼠 H-2 主要组织相容性复合体或 MHC 控制着多种 产品和特性的定义对于理解很重要 基本的遗传和免疫机制，以及临床 移植和抗病性的相关研究。 在后者中 H-2是人类MHC（HLA基因）的重要实验模型 复杂，因为它们具有显着的遗传和功能同源性。 这 这项研究的长期目标是通过遗传、生化和 功能方法，H-2复合物的多个基因，以便 增进我们对组织、演变和监管的理解 MHC 基因。 这项研究将特别关注内部基因 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淋巴细胞调节相互作用和补体反应 路径，分别。 应采取两种一般方法： 1) 努力 将用于检测和表征新的突变和重组，以 改进H-2遗传精细结构图谱并提供新的有用的种群 用于进一步的功能和生化研究。 经诱变剂处理的后代 将通过混合白细胞反应和单克隆抗体对父母进行筛查 细胞同种异体抗原的抗体。 变体将被表征 血清学、生化和功能方面，重点是改进 I-A、I-B、I-J、S 和 D 区域的定义。 2)结构、合成 将研究 S 区 C4 和 Slp 蛋白的加工，以 更好地定义指定其结构的遗传信息和 控制其表达的遗传和激素调节机制。 将进行肽图分析和氨基酸序列测定。 角色 细胞内加工中的蛋白水解裂解和糖基化 将审查前体。 将确定合成的组织位点。 C4 将检查Slp mRNA以探究调节机制。 非H-2基因 Slp表达的调节将进一步明确。