T cell and transgenic core

T细胞和转基因核心

基本信息

批准号：
8811408
负责人：
Eric S Huseby
金额：
$ 22.99万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8811408
关键词：
Affinity Animal Model Antigens Antiviral Agents Avidity B-Lymphocytes Biological Assay Breeding CD4 Positive T Lymphocytes CD8B1 gene Cell Lineage Cloning Collaborations Development Epitopes Equilibrium Generations Genes Goals Human Human Herpesvirus 6 Human Resources Hybridomas Immune Immunity Immunoglobulin Class Switching Individual Infection Influenza A virus Laboratories Lead Ligands Lymphocytic choriomeningitis virus Mediating Methods Molecular Biology Mus Natural Killer Cells Pathology Peptide/MHC Complex Peptides Production Protocols documentation Relative (related person)Role Services Specificity Staining method Stains System T cell response T-Cell Activation T-Lymphocyte TNFSF4 gene Training Transgenic Mice Transgenic Organisms Viral Virus Virus Diseases experience human disease member memory CD4 T lymphocyte mouse development novel programs recombinant virus research study virus development

项目摘要

The TCR and Transgenic Mouse Development Core will use our expertise in creating animal models of CD4 T cells and human disease to develop state of the art systems to study the role of CD4 T cells during viral infections and detrimental immune-mediated pathology. Core 0 will have several objectives. First, in collaboration with Dr. Welsh, Project 1, we will determine the role of TCR-pMHC affinity in provoking activated CD4 T cells to be targeted by NK cells. With Dr. Swain, Project 2, we will produce and characterize a panel of CD4 T cells specific for influenza A (lAV). These T cells will be used to understand which CD4 T cells are activated during anti-viral immunity, and will also be used with Dr. Stern, Core B to identify novel viral epitopes and to aid in the development of virus-specific pMHC class II tetramers. lAV specific TCRs will be cloned and a novel set of transgenic mice expressing anti-viral TCRs will be created. These new virus-specific TCR Tg mice will be used by Projects 1, 2, and 3 to study anti-viral T cell responses. In collaboration with Dr. Swain and Dr Stern, we will evaluate the role of TCfR-pMIHC affinity in CD4 T cell lineage differentiation and function following lAV infection. We have extensive experience generating T cell hybridomas, cloning TCRs and producing TCR Tg mice. Additional experiments with Dr. Selin, Project 3, will identify mechanisms that cause of cross-reactive CDS T cells to become pathogenic. Experiments with Dr. Selin and Dr. Stern, Projects 3 and 4, will use our- TCR cloning methods and T cell expression systems to characterize human TCRs specific for lAV and HHV-6. The final objective of Core C is to minimize duplicate breeding programs by centralizing the breeding of TCR Tg mice.

TCR 和转基因小鼠开发核心将利用我们在创建 CD4 T 细胞和人类疾病动物模型方面的专业知识来开发最先进的系统，以研究 CD4 T 细胞在病毒感染和有害的免疫介导的病理过程中的作用。 Core 0 将有几个目标。首先，在项目 1 中，我们将与 Welsh 博士合作，确定 TCR-pMHC 亲和力在激发激活的 CD4 T 细胞被 NK 细胞靶向的过程中的作用。在项目 2 中，我们将与 Swain 博士一起生产一组针对甲型流感 (lAV) 的 CD4 T 细胞并对其进行表征。这些 T 细胞将用于了解哪些 CD4 T 细胞在抗病毒免疫过程中被激活，还将与 Core B 的 Stern 博士一起使用来识别新的病毒表位并帮助开发病毒特异性 pMHC II 类四聚体。将克隆 IAV 特异性 TCR，并创建一组表达抗病毒 TCR 的新型转基因小鼠。项目 1、2 和 3 将使用这些新型病毒特异性 TCR Tg 小鼠来研究抗病毒 T 细胞反应。我们将与 Swain 博士和 Stern 博士合作，评估 TCfR-pMIHC 亲和力在 IAV 感染后 CD4 T 细胞谱系分化和功能中的作用。我们在生成 T 细胞杂交瘤、克隆 TCR 和生产 TCR Tg 小鼠方面拥有丰富的经验。 Selin 博士的其他实验（项目 3）将确定导致交叉反应 CDS T 细胞致病的机制。 Selin 博士和 Stern 博士的实验，项目 3 和 4，将使用我们的 TCR 克隆方法和 T 细胞表达系统来表征对 IAV 和 HHV-6 具有特异性的人类 TCR。 Core C 的最终目标是通过集中繁育 TCR Tg 小鼠来最大程度地减少重复繁育计划。