STRUCTURAL STUDY OF HLA-DQ2 AND AN ASSOCIATED COMPLEX

HLA-DQ2 及相关复合物的结构研究

• 批准号: 8362031
• 负责人: IRIMPAN I MATHEWS
• 金额: $ 0.38万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362031
• 关键词: Alleles; Barley; CD4 Positive T Lymphocytes; Celiac Disease; Chromosomes, Human, Pair 6; Complex; Disease; Epitopes; Funding; Genes; Gliadin; Gluten; Grant; HLA Antigens; Haplotypes; Histocompatibility Antigens Class II; Human; Immune response; Intestines; Major Histocompatibility Complex; National Center for Research Resources; Patients; Peptides; Predisposition; Principal Investigator; Proteins; Radiation; Research; Research Infrastructure; Resources; Rye cereal; Small intestine mucous membrane; Source; T-Lymphocyte; United States National Institutes of Health; Variant; Wheat; base; cost; glutenin; insight; structural biology

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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 这项研究旨在了解HLA-DQ2与其他分子相互作用的机制。 在6号染色体上编码的人类主要组织相容性复合物（MHC）与许多免疫病理疾病的易感性有关。与特定的MHC等位基因相关性最强的疾病之一是腹腔疾病，为此，还对人类白细胞抗原（HLA）关联的基础也有机械洞察力。腹腔疾病是由对小麦面筋（由麦醇糖和麸质亚组成部分组成）和黑麦和大麦相关蛋白质的不适当肠道免疫反应引起的。乳糜泻的患者在小肠粘膜中患有麸质反应性CD4+ T细胞，但健康对照没有。 大多数患有乳糜泻的患者携带HLA-DQ2变体DQ2.5，由DQA1*0501和DQB1*0201 DR3-DQ2单倍型编码。剩下的少数患者中的大多数表达HLA-DQ8。乳糜泻患者的麸质反应性T细胞识别出在DQ2.5或DQ8 MHC分子的背景下呈现的多种麸质表位，但在患者表达的其他MHC II类分子的背景下不明显。因此，DQ2.5和DQ8分子对麸质肽的“优先”表示似乎解释了HLA与乳糜泻的关联。