Cellular Immunity to Category A-C Viruses in Humans

描述(由申请人提供)：拟建的华盛顿大学马萨诸塞州大学人类免疫学和生物防御翻译研究中心是一个全面的跨部门合作中心，作为其总体科学主题，旨在解决人类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(包括转化为临床研究)方面具有丰富经验的高级和初级研究人员，并围绕以下部分组成：项目1(痘病毒)将确定牛痘病毒的人类免疫优势T细胞表位作为疫苗效力的标志，并促进改进天花疫苗的开发。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类免疫反应。项目3(黄病毒)将确定人类T细胞对连续病毒感染的保护性和免疫病理交叉反应。技术开发部门(TDC)将开发新的固相阵列和蛋白质组学技术，用于T细胞表位识别、病毒特异性T细胞的检测和计数，以及保护性或病理性T细胞反应的生物标记物的识别。核心设施将提供流式细胞术、MHC I类生产、MHC II类生产以及项目管理服务，供研究项目和贸易发展局使用。一个试点项目部分将支持为密歇根州立大学教职员工提出的有前途的新研究概念提供试点资金。教育部分将支持对非中心调查人员的短期培训。拟议的中心将处理NIAID与这些生物防御病原体相关的重要研究优先事项，以及年轻研究人员的职业发展。该中心将促进不同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，这将极大地提高整体研究生产率。

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.