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: 3480699
• 负责人: DONALD C. SHREFFLER
• 金额: $ 40.24万
• 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/3480699
• 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控制着一组不同的免疫反应。 其定义对于理解重要的产品和特征 基本的遗传和免疫机制，以及临床上 移植和抗病的相关研究。 在后一 背景下，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。 的 这项研究的长期目标是解决，通过遗传，生化和 功能方法，H-2复合物的多个基因，以 促进我们对组织的理解，演变和监管 MHC基因。 这项研究将特别集中在基因的内部 H-2复合物的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，分别。 一般采取两种方法：1）努力 将用于检测和表征新的突变和重组， 改进H-2遗传精细结构作图并提供新的有用的股票 用于进一步的功能和生物化学研究。 诱变剂处理的后代 父母将通过混合白细胞反应和单克隆抗体筛选 细胞同种异体抗原的抗体。 将对变体进行表征 血清学、生物化学和功能学，重点是改善 I-A、I-B、I-J、S和D区域的定义。 2)结构，合成 并研究S区C4和Slp蛋白的加工， 更好地定义指定其结构的遗传信息， 控制其表达的遗传和激素调节机制。 将进行肽图谱和氨基酸序列测定。 的角色 蛋白水解切割和糖基化在细胞内 将对前体进行检查。 将确定合成的组织部位。 C4 和Slp mRNA将被检查以探测调节机制。 非H-2基因 调节Slp表达将进一步定义。