论文标题
纵向高通量TCR曲目分析揭示了轻度Covid-19感染后T细胞记忆形成的动力学
Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection
论文作者
论文摘要
Covid-19是由SARS-COV-2冠状病毒引起的全球大流行。 T细胞通过杀死感染细胞并促进病毒特异性抗体的选择，在自适应抗病毒免疫反应中起关键作用。然而，SARS-COV-2特异性T细胞反应的动力学和交叉反应性以及由此产生的免疫记忆的多样性都尚未得到充分了解。在这项研究中，我们使用纵向高通量T细胞受体（TCR）测序来跟踪两例轻度COVID-COVID-19之后，跟踪T细胞库的变化。在两个供体中，我们都鉴定出感染后具有短暂克隆膨胀的CD4+和CD8+ T细胞克隆。 MHC四聚体结合和在SARS-COV-2表位特异性TCR的大数据库中证实了CD8+ TCR序列对SARS-COV-2表位的抗原特异性证实。我们描述了COVID-19反应克隆TCR序列中的特征基序，并在Covid-19患者的公开可用的大型曲目数据集中表现出这些基序的优先出现。我们表明，在两个捐助者中，大多数感染反应性克隆型都会获得记忆表型。在感染前的时间点，在记忆分数中检测到某些T细胞克隆，这表明预先存在的交叉反应记忆T细胞参与了对SARS-COV-2的免疫反应中。
COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. T cells play a key role in the adaptive antiviral immune response by killing infected cells and facilitating the selection of virus-specific antibodies. 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 (TCR) sequencing to track changes in the T cell repertoire following two mild cases of COVID-19. In both donors we identified CD4+ and CD8+ T cell clones with transient clonal expansion after infection. The antigen specificity of CD8+ TCR sequences to SARS-CoV-2 epitopes was confirmed by both MHC tetramer binding and presence in large database of SARS-CoV-2 epitope-specific TCRs. We describe characteristic motifs in TCR sequences of COVID-19-reactive clones and show preferential occurence of these motifs in publicly available large dataset of repertoires from COVID-19 patients. We show that in both donors the majority of infection-reactive clonotypes acquire memory phenotypes. Certain T cell clones were detected in the memory fraction at the pre-infection timepoint, suggesting participation of pre-existing cross-reactive memory T cells in the immune response to SARS-CoV-2.
