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Genome-wide fine-mapping of H. pylori-stimulated human T cell responses

幽门螺杆菌刺激的人类 T 细胞反应的全基因组精细图谱

基本信息

批准号：
8378743
负责人：
STEVEN F MOSS
金额：
$ 64.3万
依托单位：
UNIVERSITY OF RHODE ISLAND
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-01 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8378743
关键词：
Address Antigens Autoimmunity Autologous B-Lymphocytes Binding Biological Assay Biopsy Biopsy Specimen Blood Blood Flow Cytometry Blood specimen Cells Computer Simulation Data Dendritic Cells Doctor of Philosophy Environment Epitope Mapping Epitopes Flow Cytometry Frequencies Gastric Tissue Gastritis Genome Goals HLA Antigens Helicobacter Infections Helicobacter pylori Histologic Histopathology Homologous Gene Host Defense Human Human Genome Human Microbiome Human body Immune response Immune system Immunity Immunologist Immunology Infection Inflammation Inflammatory Inflammatory Response Informatics Investigation Lead Liposomes Longevity Malignant Neoplasms Maps Measures Methodology Microbe Mining Molecular Mosses Mouse Strains Mus Pathology Peptides Peripheral Blood Mononuclear Cell Phenotype Proteins Research Research Personnel Research Project Grants Sequence Homologs Services Stomach T cell response T-Lymphocyte T-Lymphocyte Epitopes Testing Therapeutic Time Tissue Sample Tissues Transgenic Mice Transgenic Organisms Ursidae Family Vaccination Vaccines Validation Work antigen binding base cytokine experimental analysis genome-wide human subject immunogenic immunogenicity in vivo insight lymph nodes meetings microorganism mouse model novel pathogen peripheral blood prevent programs prophylactic response technology development therapeutic vaccine tool vaccine candidate vaccine development vaccine evaluation

项目摘要

This U19 TRIAD Research Project proposal aims to characterize the human T cell response to H. pylori infection in order to develop a vaccine. The strategy employed involves informatic analysis of the H. pylori genome to discover potential T-cell epitopes that will be validated by experimental methodologies in vivo in humanized transgenic mice and ex vivo with gastric tissue and peripheral blood mononuclear cells from H. pylori-infected human subjects. We will discover epitopes that elicit inflammatory responses and investigate how others, which bear similarity to human genome and human microbiome sequences/may assist H. pylori to evade a protective immune response. This project will interface with the TRIAD Toolkit Core for in silico epitope mapping and HLA binding validation of computational predictions. It will also make extensive use of the TRIAD CMI Core services including the HLA transgenic mouse colony, analysis of antigen-specific T cell frequency by ELISpot, and cytokine profiling and multi-functional T cell analysis using flow cytometry. We expect to identify vaccine candidates that lead to protective human responses and plan to interface with the TRIAD Technology Development Project to produce and test a pilot dendritic cell-targeted vaccine with epitopes identified here.

这个U19 TRIAD研究项目提案旨在描述人类T细胞对H.幽门为了研制出疫苗所采用的策略包括信息分析的H。幽门基因组来发现潜在的T细胞表位，这些表位将通过体内实验方法来验证，人源化转基因小鼠和离体胃组织和外周血单核细胞从H. 幽门感染的人类受试者。我们将发现引发炎症反应的表位，并研究其他与人类基因组和人类微生物组序列相似的基因如何帮助H.幽门来逃避保护性免疫反应该项目将与TRIAD Toolkit Core接口，用于计算机模拟表位作图和计算预测的HLA结合验证。它还将广泛利用 TRIAD CMI核心服务包括HLA转基因小鼠集落、抗原特异性T细胞分析通过ELISpot的频率，以及使用流式细胞术的细胞因子谱和多功能T细胞分析。我们预计将确定导致保护性人类反应的候选疫苗，并计划与 TRIAD技术开发项目，生产和测试一种试验性树突状细胞靶向疫苗，在此识别的表位。