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

这项U19三联体研究项目提案旨在表征人类T细胞对幽门螺杆菌的反应 感染才能研制出疫苗。所采用的策略包括幽门螺杆菌的信息分析 基因组将发现潜在的T细胞表位，将在体内通过实验方法学进行验证 人源化转基因小鼠和体外培养的H。 幽门螺杆菌感染者。我们将发现引发炎症反应的表位，并研究 与人类基因组和人类微生物组序列相似的其他基因如何帮助幽门螺杆菌 以逃避保护性免疫反应。该项目将接口的三合一工具包核心在硅胶 表位映射和计算预测的人类白细胞抗原结合验证。它还将广泛利用 核心服务包括人类白细胞抗原转基因小鼠克隆、抗原特异性T细胞分析 ELISpot分析频率，流式细胞仪分析细胞因子谱和多功能T细胞。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 三合会技术开发项目将生产和测试一种树突状细胞靶向疫苗 在这里确定的表位。

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.