Cellular Immunity to Category A-C Viruses in Humans

描述（由申请人提供）：拟建的UMASS人类免疫学和生物防御转化研究中心是一个全面的，跨部门合作的研究中心，其总体科学主题是人类T淋巴细胞反应在a - c类病毒病原体的免疫发病机制和保护中的作用。该中心包括在人类免疫学和生物防御病原体研究方面具有重要专业知识的高级和初级研究人员，包括转化为临床研究，并围绕以下组成部分进行组织：项目1（痘病毒）将确定牛痘病毒的免疫显性人类T细胞表位作为疫苗效力的标记，并推进改进天花疫苗的开发知识。项目2（汉坦病毒）将定义与肾综合征出血热免疫发病机制相关的人体免疫反应。项目3（黄病毒）将定义对顺序病毒感染的保护性和免疫病理交叉反应性人T细胞反应。技术开发组件（TDC）将开发新的固相阵列和蛋白质组学技术，用于T细胞表位鉴定，病毒特异性T细胞的检测和枚举，以及保护性或病理性T细胞反应的生物标志物鉴定。核心设施将提供流式细胞术、MHC I类生产、MHC II类生产和项目管理服务，供研究项目和TDC使用。试点项目部分将支持由UMMS教师提出的有前途的新研究概念的试点资金。教育部分将支持非中心调查人员的短期培训。拟议中的中心将处理与这些生物防御病原体相关的重要NIAID研究重点以及年轻研究人员的职业发展。该中心将促进各研究人员之间的协同互动，通过定期的内部和外部审查进行评估，这将大大提高整体研究效率。

DESCRIPTION (provided by applicant): The proposed UMASS Center for Translational Research on Human Immunology and Biodefense is a comprehensive, interdepartmental collaboration to address, as its overall scientific theme, the role of human T lymphocyte responses in the immunopathogenesis of and protection from category A-C viral pathogens. The Center encompasses senior and junior investigators with significant prior expertise in human immunology and research on biodefense pathogens, including translation to clinical studies, and is organized around the following components: Project 1 (Poxviruses) will define immunodominant human T cell epitopes of vaccinia virus as markers of vaccine efficacy and advance knowledge toward the development of improved smallpox vaccines. Project 2 (Hantaviruses) will define human immune responses associated with immunopathogenesis of hemorrhagic fever with renal syndrome. Project 3 (Flaviviruses) will define protective and immunopathological cross-reactive human T cell responses to sequential virus infections. The Technical Development Component (TDC) will develop novel solid-phase array and proteomics technologies for application in T cell epitope identification, detection and enumeration of virus-specific T cells, and identification of biomarkers of protective or pathological T cell responses. Core facilities will provide flow cytometry, MHC class I production, MHC class II production, and program administration services for use by the research projects and TDC. A Pilot Projects component will support pilot funding of promising novel research concepts proposed by UMMS faculty. An Education component will support short-term training of non-Center investigators. The proposed Center will address important NIAID research priorities related to these biodefense pathogens as well as career development for young investigators. The Center will facilitate synergistic interactions between the various investigators, to be assessed by periodic internal and external review that will greatly enhance the overall research productivity.