Antigen-specific CD4+ T cells exhibit distinct transcriptional phenotypes in the lymph node and blood following vaccination in humans

Abstract: SARS-CoV-2 infection and mRNA vaccination induce robust CD4+ T cell responses that are critical for the development of protective immunity. Here, we evaluated spike-specific CD4+ T cells in the blood and draining lymph node (dLN) of human subjects following BNT162b2 mRNA vaccination using single-cell transcriptomics. We analyze multiple spike-specific CD4+ T cell clonotypes, including novel clonotypes we define here using Trex, a new deep learning-based reverse epitope mapping method integrating single-cell T cell receptor (TCR) sequencing and transcriptomics to predict antigen-specificity. Human dLN spike-specific T follicular helper cells (TFH) exhibited distinct phenotypes, including germinal center (GC)-TFH and IL-10+ TFH, that varied over time during the GC response. Paired TCR clonotype analysis revealed tissue-specific segregation of circulating and dLN clonotypes, despite numerous spike-specific clonotypes in each compartment. Analysis of a separate SARS-CoV-2 infection cohort revealed circulating spike-specific CD4+ T cell profiles distinct from those found following BNT162b2 vaccination. Our findings provide an atlas of human antigen-specific CD4+ T cell transcriptional phenotypes in the dLN and blood following vaccination or infection.

More Information:

Preprint: Research Square.

Sample information: data_inventory.csv file.

Code code_github_repo.zip or at the original github repo

Interactive Portal: CellPilot

摘要：严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）感染与mRNA疫苗接种均可诱导强烈的CD4+ T细胞应答，这类应答对于保护性免疫的建立至关重要。本研究利用单细胞转录组学技术，对BNT162b2 mRNA疫苗接种后人体血液及引流淋巴结（dLN）中的刺突蛋白特异性CD4+ T细胞进行了分析。我们对多种刺突蛋白特异性CD4+ T细胞克隆型展开研究，其中包括本研究通过Trex（一种基于深度学习的反向表位映射新方法）定义的新型克隆型——该方法整合了单细胞T细胞受体（TCR）测序与转录组学数据以预测抗原特异性。
人体引流淋巴结中的刺突蛋白特异性滤泡辅助T细胞（TFH）呈现出独特的表型特征，包括生发中心（GC）-TFH与IL-10+ TFH，且这些表型在生发中心应答过程中随时间动态变化。配对TCR克隆型分析显示，尽管两个组织区域中均存在大量刺突蛋白特异性克隆型，但循环系统与引流淋巴结的克隆型呈现出组织特异性分离。对另一组SARS-CoV-2感染队列的分析表明，循环系统中的刺突蛋白特异性CD4+ T细胞转录特征与BNT162b2疫苗接种后所观察到的特征存在显著差异。本研究的结果构建了疫苗接种或感染后人体引流淋巴结与血液中抗原特异性CD4+ T细胞转录表型图谱。

补充信息：
预印本：发布于Research Square平台。
样本信息：详见data_inventory.csv文件。
代码：可通过code_github_repo.zip获取，或前往原始GitHub仓库获取。
交互式分析门户：CellPilot