MHC Proteins and Human Disease

描述(由申请者提供)：已经了解了很多关于 近三十年来人类组织相容性抗原的结构与功能 好几年了。一些细节仍有待澄清，但除此之外，信息 可以用来探索这些蛋白质与 人类疾病。本申请的具体目标是： 1.利用人类基因建立寻常型天疱疮小鼠模型 使用这些模型来识别与人类结合的疾病相关多肽表位 第11类MHC蛋白。 2.探讨人类白细胞抗原-DP(Ⅱ类MHC蛋白)与Hard的关系 金属疾病。 3.研究人类白细胞抗原-B27分子子集(A)的反应性基础 与强直性脊柱炎有关的I类MHC蛋白)，具有不寻常的 单抗Marb-4以及这个亚群是否可能与 疾病。 4.检查共聚物1在治疗中的有效性基础 多发性硬化症[与第II类MHC蛋白人类白细胞抗原-DR2基因有关 (DRB1*1501)]并研究更有效的共聚物 可以设计用于治疗这种疾病，也可以用于治疗 自身免疫性疾病(即类风湿性关节炎)。 5.利用寡聚化T细胞表位研究多发性骨髓瘤小鼠模型 硬化症和寻常型天疱疮，这两种疾病都与特定的等位基因有关 第二类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.