Structural studies of the human class II MHC proteins.

人类 II 类 MHC 蛋白的结构研究。

• 批准号: 6526283
• 负责人: RUIZ Z ZAVALA
• 金额: $ 2.68万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6526283
• 关键词: Escherichia coli; MHC class II antigen; T lymphocyte; antigen presentation; conformation; dendrites; enzyme linked immunosorbent assay; gel filtration chromatography; human tissue; immunoaffinity chromatography; leukocyte activation /transformation; microglia; nuclear magnetic resonance spectroscopy; protein binding; protein structure function; relaxation spectrometry; synthetic peptide

DESCRIPTION (provided by applicant): The broad long-term objective of the proposed research is to understand the conformational changes in major histocompatibility complex (MHC) proteins and their role in antigen presentation. The specific aims of the proposed research are to obtain structural information on empty and peptide-loaded forms of the human MHC protien, HLA-DR1, and to characterize the two empty forms of HLA-DR1 observed in kinetics experiments. Kinetics studies have indicated that the empty protein exists in two conformations in equilibrium: one peptide-receptive and one unable to bind peptide, peptide-averse. A mixture of these two conformations was previously used to characterize the difference between empty and peptide-loaded HLA-DR1. In the proposed research, I will determine the regions of HLA-DR1 that are responsible for the conformational change upon peptide binding with the use of NMR spectroscopy. Using a variety of bio-physical methods we will try to characterize differences between the peptide-receptive and peptide-averse forms of empty HLA-DR1. The health relatedness of this research is that the information, gathered will refine the current model for peptide binding of MHC class II and help in the development of synthetic peptides for potential use in disease treatment and in the identification of potential autoimmune antigens.

描述（由申请人提供）：广泛的长期目标， 建议的研究是了解主要的构象变化， 组织相容性复合体（MHC）蛋白及其在抗原中作用 演示文稿.拟议研究的具体目标是获得 人MHC的空和肽负载形式的结构信息 蛋白，HLA-DR 1，并表征观察到的两种空形式的HLA-DR 1 在动力学实验中。动力学研究表明， 存在于两种平衡构象中：一种是肽受体，另一种是肽受体。 不能结合肽，肽厌恶。这两种构象的混合物 以前用于表征空和 负载肽的HLA-DR 1。在建议的研究中，我将确定区域 HLA-DR 1的分子，负责肽的构象变化 结合使用核磁共振光谱。利用各种生物物理 方法，我们将尝试表征肽受体之间的差异， 和空HLA-DR 1的肽厌恶形式。这与健康的关系 研究是，收集的信息将完善目前的模型， 肽结合MHC II类，并帮助开发合成 用于疾病治疗和鉴定 潜在的自身免疫抗原