IMMUNOBIOLOGY OF THE MAJOR HISTOCOMPATIBILITY COMPLEX

主要组织相容性复合体的免疫生物学

• 批准号: 3132027
• 负责人: MARCIA M MILLER
• 金额: $ 11.36万
• 依托单位: CITY OF HOPE NATIONAL MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-02-01 至 1988-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3132027
• 关键词: animal population genetics; biological polymorphism; erythroid stem cell; gene expression; genetic library; genetic manipulation; genetic recombination; immune response genes; linkage mapping; major histocompatibility complex; molecular cloning; nucleic acid sequence; surface antigens

The recent findings that many more class I genes may be present within the major histocompatibility complex (MHC) than previously thought, and the emerging evidence that many of these genes encode tissue differentiation antigens, some of which may function in cell recognition outside the immune system, make it appropriate to look more intently at differentiation antigens, some of which may function in cell recognition outside the immune system, make it appropriate to look more intently at differentiation antigens encoded by the MHC. Among these differentiation antigens are highly polymorphic erythroid cell antigens encoded by the chicken MHC. These enigmatic antigens, the B-G antigens, have formed the basis of MHC typing in chickens from the time that the chicken MHC or B system of histocompatibility was first identified. We have purified and analyzed the B-G antigen from the one haplotype, B21, and have found evidence that B-G antigens may be unusual variants of MHC class I molecules. I propose to determine the molecular structure of the B-G 21 antigen in order to better understand the similarities and differences which exist between these polymorphic differentiation antigens and class I transplantation antigens. Microsequencing, tryptic peptide mapping and gene sequencing will be used to determine the structure of the B-G 21 antigen. Genomic and cDNA libraries will be prepared from which the B-G21 antigen gene will be cloned. The B21 class I gene(s) will also be isolated using murine class I gene probes and the sequence of this gene used in the comparative analysis of B-G21. These two genes will be mapped with respect to each other. The low frequency of recombination between them indicates they are closer to each other than many elements within the murine MHC. The basis of the polymorphism of the B-G antigens will be examined using suitable recombinant DNA probes derived from the cloned B-G21 gene. These data will help us to understand the organization and evolution of the MHC.

最近的发现表明，更多的I类基因可能存在于 主要组织相容性复合体(MHC)比之前认为的要好，而且 越来越多的证据表明，这些基因中的许多编码组织分化 抗原，其中一些可能在免疫外的细胞识别中发挥作用 系统，使得更专注地看待差异化是合适的 抗原，其中一些可能在免疫外的细胞识别中发挥作用 系统，使得更专注地看待差异化是合适的 由MHC编码的抗原。在这些分化抗原中有 鸡MHC编码的高度多态的红系细胞抗原。 这些神秘的B-G抗原构成了MHC的基础 从鸡的MHC或B系统的时间开始分型 首先对组织相容性进行鉴定。我们已经提纯和分析了 来自一种单倍型B21的B-G抗原，并发现证据表明B-G 抗原可能是MHC I类分子的不寻常变体。我提议 确定B-G21抗原的分子结构，以便更好地 了解它们之间存在的异同 多态分化抗原和I类移植抗原。 将使用微测序、胰酶多肽图谱和基因测序 确定B-G21抗原的结构。基因组学与基因工程 将准备B-G21抗原基因的文库 克隆的。B21 I类基因(S)也将用小鼠I类基因分离 用于比较分析的基因探针和该基因的序列 B-G21。这两个基因将被相互映射。这个 它们之间的低频率重组表明它们更接近于 相互之间比小鼠MHC中的许多元素更重要。的基础是 B-G抗原的多态将用适当的 从克隆的B-G21基因衍生的重组DNA探针。这些数据将 帮助我们了解MHC的组织和演变。