Dissecting the SARS-CoV2-specific immune response by epitope and single cell mapping in differentially affected individuals

通过表位和单细胞图谱分析不同受影响个体的 SARS-CoV2 特异性免疫反应

• 批准号: 457497863
• 负责人: Professor Dr. Rafael Kramann
• 金额: --
• 依托单位: Institut für Experimentelle Innere Medizin und Systembiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2021
• 资助国家: 德国
• 起止时间: 2020-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/457497863?language=en
• 关键词: Dissecting; SARS; CoV2; specific; immune

While many countries are facing a second wave of infection, the exact immunological pathomechanism that causes a small percentage of infected patients to suffer particularly severe and complicated courses of disease, remains unclear. In order to uncover the immunological basis of the severe courses of the disease, we will perform screening experiments using MHC-Dextramer embedded SARS-CoV2 epitopes to identify the most immunogenic virus epitopes comparing differentially affected patients and healthy probands. In a second step we will use these identified epitopes to dissect the T-cell response of antigen-specific and non-antigen-specific T cells at a single cell level, including T cell receptor sequencing and 5´single cell RNA-sequencing. We will compare patients with asymtopmatic infection to moderate and severe COVID-19 disease and healthy probands. The overall aim of the study is to generate a precise map of the T-cell response against the SARS-CoV2 virus. This data will be not only important to understand the disease but similar important guide drug repurposing and development as well as vaccine development.

虽然许多国家正面临第二波感染，但导致一小部分受感染患者出现特别严重和复杂病程的确切免疫病理机制仍不清楚。为了揭示严重病程的免疫学基础，我们将使用MHC-Dextramer嵌入SARS-CoV 2表位进行筛选实验，以确定最具免疫原性的病毒表位，比较不同的受影响患者和健康先证者。在第二步中，我们将使用这些鉴定的表位在单细胞水平上剖析抗原特异性和非抗原特异性T细胞的T细胞应答，包括T细胞受体测序和5 '单细胞RNA测序。我们将比较无症状感染患者与中度和重度COVID-19疾病和健康先证者。 该研究的总体目标是生成针对SARS-CoV 2病毒的T细胞反应的精确图谱。这些数据不仅对了解这种疾病很重要，而且对指导药物的再利用和开发以及疫苗的开发也很重要。