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IMMUNOBIOLOGY OF THE MAJOR HISTOCOMPATIBILITY COMPLEX

主要组织相容性复合体的免疫生物学

基本信息

批准号：
3132029
负责人：
MARCIA M MILLER
金额：
$ 15.21万
依托单位：
BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-02-01 至 1992-12-31
项目状态：
已结题

项目摘要

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鸟类主要组织相容性复合体（MHC）可以告诉我们 MHC基因复合体的进化以及这种进化的方式， MHC赋予抗病性。这项研究提供了一个有机会对比非哺乳动物MHC的结构，鸡的B系统，小鼠和人的MHC。已知一个B系统子区域，B-G子区域，编码不同于已知基因产物的抗原与哺乳动物的MHC有关。虽然这些抗原高度多态性，其基因与在B系统内编码的I类和II类抗原，它们是明显不同于所有其他MHC编码的分子。部分从本实验室分离的B-B cDNa克隆中获得的序列数据，表明B-G抗原含有一个结构域，类似于免疫球蛋白和T细胞受体可变区结构域（识别结构域）比Ig-恒定区结构域例如在I类和II类抗原中发现的那些。 B系统的另一个重要方面是发现B-F/B-L亚区的存在与马立克氏病是一种疱疹病毒引起的疾病，淋巴瘤因此，B系统提供了一个研究模型 MHC与病毒性疾病之间的关系试剂变得可用。具体目标是：1）完成对 B-G21抗原，产生B-G gubregion并将B-G连接到B-F和B-L子区域; 2）连接到进行B-F21和B-L21基因的分子克隆，对这些B亚区进行类似的分子遗传学分析，编码禽类I类和II类基因对应物，和 3)我们希望开始应用在本研究旨在探讨感染过程，马立克氏病病毒引起的肿瘤。