IMMUNOBIOLOGY OF THE HEMOPOIETIC HISTOCOMPATIBILITY

造血组织相容性的免疫生物学

• 批准号: 3181777
• 负责人: ICHIRO NAKAMURA
• 金额: $ 12.78万
• 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/3181777
• 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

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.

该提案的目的是剖析鲜为人知的机制， 小鼠对正常和恶性造血的潜在天然抵抗力 细胞，矛盾的是，它在 F1 杂交受体中表现出来 亲本移植物（杂交抗性）并由自然杀伤剂（NK）介导 细胞样效应器。 假定的靶细胞表面的表达 结构及其被效应器的识别，是免疫遗传学的 特定的并由一类看似“非共显性”的基因控制 有限的多态性，即 Hh（造血组织相容性） 基因。 本研究的主要目的是应用 分子遗传学技术来了解杂种的遗传基础 抗性由 Hh 位点之一 Hh-1 控制，该位点映射到 第 17 号染色体的 H-2D 区域。 两个替代假设可能 解释“非共显性”将主要通过 DNA 介导的基因进行测试 转移;非共显性表达的顺式作用机制是 如果 Hh-1- 表型通过以下方式转换为 Hh-1+ 表型，则支持 用来自 Hh-1+ 小鼠品系的 DNA 转染 Hh-1- 细胞，而 如果出现以下情况，就会涉及非共显性的反式作用遗传机制： Hh-1 表达可通过从 Hh-1- 转移 DNA 分子来抑制 应变进入 Hh-1+ 细胞。 通过这种方法，H-2D 区域基因 编码或调节Hh-1控制结构的表达可以是 已识别并隔离。 最终，这些细胞表面的性质 目标结构及其在正常和异常情况下的表达和功能 （白血病）造血和 Nk 样细胞的生理作用 认识到这种结构，可以定义。 因此，这项研究应该 帮助阐明该专业的一个重要的、可能是监管的功能 一类淋巴细胞的组织相容性复合物和真实功能， 即 NK 细胞。