MHC Proteins and Human Disease

描述（由申请人提供）：已经了解了很多关于 人类组织相容性抗原的结构与功能 年一些细节仍有待澄清，但除此之外， 已经获得的可以用来探索这些蛋白质与 人类疾病。本申请的具体目的是： 1.目的：利用人类基因建立寻常型天疱疮小鼠模型， 使用这些模型来鉴定与人类结合的疾病相关的肽表位， 11类MHC蛋白。 2.目的探讨HLA-DP（MHC Ⅱ类蛋白）与Hard的关系。 金属疾病 3.为了研究HLA-B27分子亚群（a）的反应性基础， 与强直性脊柱炎相关的I类MHC蛋白）， 单克隆抗体MARB-4以及该亚群是否可能与 疾病 4.检查共聚物1在治疗中的有效性的基础 多发性硬化症[与II类MHC蛋白HLA-DR 2遗传相关 (DRB1*1501）]，并检查更有效的共聚物 可以设计用于治疗这种疾病，以及治疗 自身免疫性疾病（即类风湿性关节炎）。 5.为了利用寡聚化T细胞表位来研究小鼠模型， 硬化症和寻常天疱疮，两者都与特定的等位基因有关， II类MHC基因。

DESCRIPTION (provided by applicant): A great deal has been learned about the structure and function of human histocompatibility antigens in the past thirty years. Some details remain to be elucidated but, in addition, the information already obtained can be used to explore the relationship of these proteins to human diseases. The specific aims of this application are: 1. To develop murine models of pemphigus vulgaris employing human genes and to use these models to identify disease-related peptide epitopes bound to human Class 11 MHC proteins. 2. To examine the relationship between HLA-DP (a Class II MHC protein) and Hard Metal Diseases. 3. To examine the basis of the reactivity of a subset of HLA-B27 molecules (a class I MHC protein linked to ankylosing spondylitis) with an unusual monoclonal antibody MARB-4 and whether this subset might be related to the disease. 4. To examine the basis for the effectiveness of Copolymer 1 in the treatment of multiple sclerosis [genetically linked to the Class II MHC protein HLA-DR2 (DRB1*1501)] and to examine the possibility that more effective copolymers could be designed for the therapy of this disease, as well as for the therapy of the autoimmune disease (i.e. rheumatoid arthritis). 5. To utilize oligomerized T cell epitopes to study mouse models of, multiple sclerosis and pemphigus vulgaris, both of which are linked to specific alleles of Class II MHC genes.