Structure and function of peptide presentation by CD1d

CD1d 肽呈递的结构和功能

• 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
• 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

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）上的抗原受体检测抗原，例如抗原呈递细胞表面上存在的抗原呈递分子所呈递的肽或糖脂。称为主要组织相容性蛋白的抗原呈递分子已经进化为呈递肽，而结构相关的CD 1家族已经进化为结合糖脂，糖脂结合在深的疏水结合槽中。在TCR与MHC或CD 1结合抗原结合后，T细胞被激活，导致细胞因子（第二信使分子）的产生，在外来抗原的情况下，所述细胞因子激活其它免疫细胞以进行完全免疫应答来对抗感染。我们已经发现，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抗原受体与由CD1d呈递的肽抗原的结合，以了解T细胞活化的结构要求。该知识将导致设计改变的肽配体，其可以被选择以增强对感染的免疫应答或改变细胞因子谱，增加促炎或抗炎细胞因子的产生，以帮助改善自身免疫疾病，如糖尿病或多发性硬化症。