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

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.

这一建议的目的是剖析鲜为人知的机制(S)， 小鼠对正常和恶性造血系统的天然抵抗力 细胞，这自相矛盾地表现在F1杂交受体中 亲本嫁接(杂交抗性)，由自然杀伤(NK)介导 细胞样的效应器。假定靶细胞表面的表达 结构及其被效应器识别，是免疫遗传的 由一类看似“非共显性”的基因所控制 有限多态，即HH(用于造血组织相容性) 基因。建议研究的主要目的是应用 分子遗传学技术研究杂交种的遗传基础 抗性由一个HH基因控制，即HH-1，它映射到 17号染色体H-2D区。两个可选的假设可能 解释“非共显性”将主要由DNA介导的基因来检验 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 用小鼠HH-1+株DNA转染HH-1-细胞 非共显性的反式作用遗传机制将被牵连在以下情况 HH-1的DNA分子转移抑制了HH-1的表达 培养成HH-1+细胞。用这种方法，H-2D区基因 编码或调节HH-1控制结构的表达可以是 被确认和隔离。最终，这些细胞表面的性质 靶结构及其在正常和异常中的表达和功能 (白血病)造血和NK样细胞的生理作用 认识到这种结构，可以被定义。因此，这项研究应该 帮助解开一个重要的，可能是监管的主要职能 一类淋巴细胞的组织相容性复合体和真实功能， 即NK细胞。