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

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遭受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SARS严重病程的免疫学基础，我们将使用MHC-DExtramer嵌入SARS-CoV2表位进行筛选实验，以确定免疫原性最强的病毒表位，比较不同感染患者和健康先证者。在第二步中，我们将使用这些已识别的表位在单个细胞水平上剖析抗原特异性和非抗原特异性T细胞的T细胞反应，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、重度新冠肺炎病患者和健康先证者的差异。这项研究的总体目标是生成针对SARS-CoV2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，而且对药物的再利用和开发以及疫苗的开发都有重要的指导意义。

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.