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.

本提案的目的是剖析鲜为人知的机制，