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: 3132030
• 负责人: MARCIA M MILLER
• 金额: $ 12.87万
• 依托单位: BECKMAN RES INST OF THE CITY OF HOPE
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1991-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3132030
• 关键词: Marek's disease; biological polymorphism; chickens; gene expression; genetic library; genetic manipulation; histocompatibility antigens; laboratory mouse; laboratory rabbit; linkage mapping; major histocompatibility complex; molecular cloning; neoplasm /cancer immunology; nucleic acid probes; nucleic acid sequence; protein structure; surface antigens; virus infection mechanism; virus related neoplasm /cancer

The long-term objective of the proposed research is to learn what the avian major histocompatibility complex (MHC) can tell us about the evolution of the MHC gene complex and the means by which this MHC confers disease resistance. The proposed study provides an opportunity to contrast the strucutre of a non-mammalian MHC, the B system of the chicken, with the MHCs of mouse and man. It is already known that one B system subregion, the B-G subregion, encodes antigens which are differrent from known gene products associated with the MHC of mammals. While these antigens are highly polymorphic and their genes tightly-linked with those of the class I and class II antigens encoded within the B system, they are clearly different from all ohter MHC-encoded molecules. partial sequence data derived from a B-B cDNa clone isolated in this labe indicates that the B-G antigens contain a domain more closely similar to immunoglobulin and T-cell receptor variable region domains (recognition domains) than to Ig-constant region domains such as those found within class I and class II antigens. Another important aspect of the B system is the particularly strong association found between the presence of the B-F/B-L subregion genes and resistance to Marek's disease, a herpesvirus-induced lymphoma. Hence, the B system provides a model in which to study the relationship between the MHC and viral disease when suitable reagents become available. The specific aims are 1) to complete a structural analysis of the B-G21 antigens, produce a restriction enzyme map of the B-G gubregion and link B-G to the B-F and B-L subregions; 2) to undertake molecular cloning of B-F21 and B-L21 genes and complete a similar molecular genetic analysis of these B subregions which encode the avian class I and class II-like gene counterparts, and 3) we would like to begin to apply the information learned in the present study to the investigation of the process of infection and tumorigenesis caused by Marek's disease virus.

拟议研究的长期目标是了解什么 禽类主要的组织相容性复合物（MHC）可以告诉我们有关 MHC基因复合物的演变及其的手段 MHC赋予抗病性。 拟议的研究提供了 将非哺乳动物MHC的融合的机会， B鸡的B系统，带有老鼠和人的MHC。 这是 已经知道一个B系统子区域B-G子区域， 编码与已知基因产物不同的抗原 与哺乳动物的MHC相关。 这些抗原是 高度多态性及其基因与该基因紧密连接 在B系统中编码的I类和II类抗原，它们是 显然与所有OHTER MHC编码的分子不同。 部分的 源自该LABE中分离的B-B cDNA克隆的序列数据 表明B-G抗原更紧密地包含一个域 类似于免疫球蛋白和T细胞受体可变区域 域（识别域）比Ig-Constant区域域 例如在I类和II类抗原中发现的。 B系统的另一个重要方面是特别强大 在B-F/B-L子区域的存在之间发现了关联 基因和对马雷克氏病的抗性，疱疹病毒引起的 淋巴瘤。 因此，B系统提供了研究模型 合适的MHC与病毒疾病之间的关系 试剂可用。 具体目的是1）完成对 B-G21抗原，产生B-G的限制酶图 gubregion并将B-G链接到B-F和B-L子区域； 2）到 承担B-F21和B-L21基因的分子克隆并完成 这些B子区域的类似分子遗传分析 编码avian I类和类似II类的基因对应物，以及 3）我们想开始应用在 目前的研究调查了感染过程 由Marek病毒引起的肿瘤发生。