Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection

COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. T cell response is a critical part of both individual and herd immunity to SARS-CoV-2 and the efficacy of developed vaccines. However, neither the dynamics and cross-reactivity of the SARS-CoV-2-specific T cell response nor the diversity of resulting immune memory are well understood. In this study, we use longitudinal high-throughput T cell receptor sequencing to track changes in the T cell repertoire following two mild cases of COVID-19 infection. In both donors, we identified SARS-CoV-2-responding CD4+ and CD8+ T-cell clones. We describe characteristic motifs in TCR sequences of COVID-reactive clones, suggesting the existence of immunodominant epitopes. We show that in both donors the majority of infection-reactive clonotypes acquire memory phenotypes. Certain CD4+ clones were detected in the memory fraction at the pre-infection timepoint, suggesting the participation of preexisting cross-reactive memory T-cells in the immune response to SARS-CoV-2.Data processing instructions are available at: https://github.com/pogorely/Minervina_COVID

新型冠状病毒肺炎（COVID-19）是由严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）引发的全球性大流行病。T细胞应答是个体免疫与群体免疫针对SARS-CoV-2，以及已研发疫苗的效力的关键组成部分。然而，目前针对SARS-CoV-2特异性T细胞应答的动态变化与交叉反应性，以及由此产生的免疫记忆多样性，仍未得到充分阐明。本研究采用纵向高通量T细胞受体（TCR）测序技术，对两例轻症COVID-19感染患者的T细胞受体库变化进行追踪。在两名受试者体内，均成功鉴定出针对SARS-CoV-2的应答性CD4+与CD8+ T细胞克隆。本研究描述了COVID反应性克隆的TCR序列特征基序，提示存在免疫显性表位。研究证实，两名受试者体内大多数感染反应性克隆型均获得了记忆细胞表型。在感染前时间点采集的记忆细胞组分中，可检测到部分CD4+克隆，这提示预先存在的交叉反应性记忆T细胞参与了针对SARS-CoV-2的免疫应答。数据处理流程可参考：https://github.com/pogorely/Minervina_COVID