IMMUNOBIOLOGY OF THE HEMOPOIETIC HISTOCOMPATIBILITY

造血组织相容性的免疫生物学

• 批准号: 3181776
• 负责人: ICHIRO NAKAMURA
• 金额: $ 12.46万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1989-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3181776
• 关键词: bone marrow transplantation; gel electrophoresis; gene expression; genetic regulation; genetic transcription; graft versus host disease; heterozygote; histocompatibility gene; homologous transplantation; hybrid cells; immunity; major histocompatibility complex; neoplasm /cancer transplantation; radioimmunoassay; surface antigens; bone marrow transplantation; gel electrophoresis; gene expression; genetic regulation; genetic transcription; graft versus host disease; heterozygote; histocompatibility gene; homologous transplantation; hybrid cells; immunity; major histocompatibility complex; neoplasm /cancer transplantation; radioimmunoassay; surface antigens

The objective of this proposal is to dissect the little known mechanism(s), underlying murine natural resistance to normal and malignant hemopoietic cells, which paradoxically manifests itself in F1 hybrid recipients of parental grafts (hybrid resistance) and is mediated by natural killer (NK) cell-like effectors. The expression of the putative target cell surface structure and its recognition by the effectors, are immunogenetically specific and controlled by a class of seemingly "noncodominant" genes of limited polymorphism, i.e., the Hh (for hemopoietic histocompatibility) genes. It is the primary purpose of the proposed study to apply the techniques of molecular genetics to understand the genetic basis of hybrid resistance controlled by one of the Hh loci, the Hh-1, that maps to the H-2D region of the 17th chromosome. Two alternative hypotheses that may explain the "noncodominance" will be tested primarily by DNA-mediated gene transfer; a cis-acting mechanism of noncodominant expression would be supported if a Hh-1- phenotype is converted to a Hh-1+ phenotype by transfecting a Hh-1- cell with DNA from Hh-1+ strain of mouse, whereas a trans-acting genetic mechanism of noncodominance would be implicated if Hh-1 expression is suppressed by transfer of a DNA molecule from a Hh-1- strain into a Hh-1+ cell. With this approach, the H-2D region gene encoding or regulating the expression of Hh-1-controlled structures can be identified and isolated. Ultimately, the nature of these cell surface target structures, their expression and function in normal and abnormal (leukemic) hemopoiesis, and a physiological role of Nk-like cells recognizing such structures, may be defined. This study, therefore, should help unravel an important, possibly regulatory, function of the major histocompatibility complex and true functions of a class of lymphoid cells, i.e., the NK cells.

该提议的目的是剖析鲜为人知的机制， 基础鼠对正常和恶性造血的自然抗性 细胞在F1的Hybrid受体中自相矛盾地表现出来 父母移植物（杂种抗性），由自然杀手（NK）介导 细胞状效应子。 推定目标细胞表面的表达 结构及其效应子的识别是免疫力学的 由一类看似“非偶氮”基因的特定和控制 有限的多态性，即HH（用于造血组织相容性） 基因。 提出的研究是应用的主要目的 分子遗传学的技术了解杂种的遗传基础 电阻由HH基因座之一HH-1控制，该位点映射到 第17染色体的H-2D区域。 两个可能的替代假设 解释“非稳态”将主要通过DNA介导的基因测试 转移;非邻不能表达的顺式作用机制将是 如果HH-1-表型通过通过 用小鼠HH-1+应变的DNA转染HH-1细胞，而A 如果不稳定的跨作用遗传机制将涉及 通过从HH-1-转移DNA分子来抑制HH-1的表达 应变成HH-1+细胞。 使用这种方法，H-2D区域基因 编码或调节HH-1控制结构的表达可以是 确定和孤立。 最终，这些细胞表面的性质 目标结构，其表达和功能在正常和异常中 （白血病）造血和NK样细胞的生理作用 可以定义识别此类结构。 因此，这项研究应该 帮助解散专业的重要（可能是调节的功能） 一类淋巴样细胞的组织相容性复合物和真实功能， 即NK细胞。