STRUCTURAL STUDY OF HLA-DQ2 AND AN ASSOCIATED COMPLEX

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 本研究旨在了解HLA-DQ 2与其他分子相互作用的机制。 人类主要组织相容性复合体（MHC），编码在6号染色体上，与许多免疫病理疾病的易感性有关。与特定MHC等位基因关联最强的疾病之一是乳糜泻，对于乳糜泻，也存在对人类白细胞抗原（HLA）关联的基础的机械见解。乳糜泻是由肠道对小麦面筋（由麦醇溶蛋白和麦谷蛋白亚组分组成）以及黑麦和大麦的相关蛋白质的不适当免疫反应引起的。乳糜泻患者的小肠粘膜中有谷蛋白反应性CD 4 + T细胞，但健康对照组没有。 大多数乳糜泻患者携带HLA-DQ 2变体DQ 2.5，其由DR 3-DQ 2单倍型的DQA 1 *0501和DQB 1 *0201基因编码。剩下的少数患者中的大多数表达HLA-DQ 8。乳糜泻患者的谷蛋白反应性T细胞识别在DQ 2.5或DQ 8 MHC分子的背景下呈现的一组不同的谷蛋白表位，但不识别患者表达的其他MHC II类分子的背景下呈现的谷蛋白表位。因此，DQ 2.5和DQ 8分子对谷蛋白肽的“优先”呈递似乎解释了HLA与乳糜泻的关联。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This study is aimed at understanding the mechanism of HLA-DQ2 interaction with other molecules. The human major histocompatibility complex (MHC), encoded on chromosome 6, is associated with susceptibility to many immunopathological diseases. One of the diseases with the strongest association with particular MHC alleles is celiac disease, for which there is also mechanistic insight into the basis for the human leukocyte antigen (HLA) association. Celiac disease is caused by an inappropriate intestinal immune response to wheat gluten (consisting of the gliadin and glutenin subcomponents) and the related proteins of rye and barley. Patients with celiac disease have gluten-reactive CD4+ T cells in their small intestinal mucosa, but healthy controls do not. Most patients with celiac disease carry the HLA-DQ2 variant DQ2.5, which is encoded by the DQA1*0501 and DQB1*0201 genes of the DR3-DQ2 haplotype. Most of the few remaining patients express HLA-DQ8. The gluten-reactive T cells of patients with celiac disease recognize a diverse set of gluten epitopes presented in context of DQ2.5 or DQ8 MHC molecules but not in the context of other MHC class II molecules expressed by the patients. 'Preferential' presentation of gluten peptides by the DQ2.5 and DQ8 molecules thus seems to explain the association of HLA with celiac disease.