Structure and function of peptide presentation by CD1d

CD1d 肽呈递的结构和功能

基本信息

批准号：
8569883
负责人：
Dirk M Zajonc
金额：
$ 24.96万
依托单位：
LA JOLLA INSTITUTE FOR IMMUNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-15 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8569883
关键词：
Accounting Affinity Amino Acid Substitution Amino Acids Anti-Inflammatory Agents Anti-inflammatory Antigen Presentation Antigen Receptors Antigen-Presenting Cells Antigens Autoimmune Diseases Binding Biological Assay Biology CD8B1 gene Cells Chemicals Chemistry Collagen Collagen Arthritis Complex Data Delayed Hypersensitivity Development Diabetes Mellitus Docking Epitopes Experimental Autoimmune Encephalomyelitis Family Flow Cytometry Future Galactosylceramides Glycine Glycolipids Histocompatibility Homologous Gene Human Hybridomas Immune Immune response Immune system Immunotherapy Infection Inflammatory Inflammatory Response Interferons Interleukin-4 Knowledge Lead Ligands Lipid Binding Lipids Lymphocyte MHC Class I Genes Measures Modification Multiple Sclerosis Mus Orthologous Gene Peptide Library Peptides Phage Display Population Production Proline Property Proteins Radioactive Recombinants Reporting Research Design Second Messenger Systems Specificity Splenocyte Staining method Stains Structure Surface Antigens Surface Plasmon Resonance T-Cell Activation T-Lymphocyte Testing Vaccination X-Ray Crystallography airway inflammation antigen binding base cytokine design in vivo killer T cell novel novel therapeutics public health relevance receptor research study second messenger

项目摘要

DESCRIPTION (provided by applicant): The immune system uses antigen receptors on T cells (TCRs) to detect antigens, such as peptides or glycolipids that are presented by antigen-presenting molecules present on the surface of antigen-presenting cells. The antigen presenting molecules, termed Major Histocompatibility proteins have evolved to present peptides, while the structurally related CD1 family has evolved to bind glycolipids that are bound in deep and hydrophobic binding grooves. Upon binding of the TCR to the MHC or CD1 bound antigen, the T cell becomes activated, leading to the production of cytokines, second messenger molecule, that activate other immune cells for a full immune response to counter an infection, in the case of foreign antigens. We have found that peptides can also be presented by CD1d, and that certain peptides can activate T cells that are considered specific for certain glycolipid antigens. Our lab uses Xray crystallography to investigate at the atomic level the binding of the antigen-receptor to the peptide antigen when presented by CD1d in order to understand the structural requirements for T cell activation. This knowledge will lead to the design of altered peptide ligands that can be selected to either enhance the immune response to infection or to change the cytokine profile, increased production of either pro- inflammatory or anti-inflammatory cytokines, to help ameliorate autoimmune diseases, such as diabetes or multiple sclerosis.

描述（由申请人提供）：免疫系统使用T细胞（TCR）上的抗原受体来检测抗原，例如由抗原呈递细胞表面上存在的抗原呈递分子呈递的肽或糖脂。被称为主要组织相容性蛋白的抗原呈递分子已进化为呈递肽，而结构相关的 CD1 家族已进化为结合糖脂，糖脂结合在深疏水性结合槽中。 TCR 与 MHC 或 CD1 结合抗原结合后，T 细胞被激活，导致产生细胞因子（第二信使分子），激活其他免疫细胞以产生全面的免疫反应，以对抗感染（如果是外源性感染）。抗原。我们发现肽也可以由 CD1d 呈递，并且某些肽可以激活被认为对某些糖脂抗原具有特异性的 T 细胞。我们的实验室使用 X 射线晶体学在原子水平上研究 CD1d 呈递时抗原受体与肽抗原的结合，以了解 T 细胞激活的结构要求。这些知识将导致设计改变的肽配体，可以选择这些配体来增强对感染的免疫反应或改变细胞因子谱，增加促炎或抗炎细胞因子的产生，以帮助改善自身免疫性疾病，例如如糖尿病或多发性硬化症。