PDF(Pubmed)
Abstract：
SARS-CoV-2 vaccines have been used worldwide to combat COVID-19 pandemic. To elucidate the factors that determine the longevity of spike (S)-specific antibodies, we traced the characteristics of S-specific T cell clonotypes together with their epitopes and anti-S antibody titers before and after BNT162b2 vaccination over time. T cell receptor (TCR) αβ sequences and mRNA expression of the S-responded T cells were investigated using single-cell TCR- and RNA-sequencing. Highly expanded 199 TCR clonotypes upon stimulation with S peptide pools were reconstituted into a reporter T cell line for the determination of epitopes and restricting HLAs. Among them, we could determine 78 S epitopes, most of which were conserved in variants of concern (VOCs). After the 2nd vaccination, T cell clonotypes highly responsive to recall S stimulation were polarized to follicular helper T (Tfh)-like cells in donors exhibiting sustained anti-S antibody titers (designated as \'sustainers\'), but not in \'decliners\'. Even before vaccination, S-reactive CD4+ T cell clonotypes did exist, most of which cross-reacted with environmental or symbiotic microbes. However, these clonotypes contracted after vaccination. Conversely, S-reactive clonotypes dominated after vaccination were undetectable in pre-vaccinated T cell pool, suggesting that highly responding S-reactive T cells were established by vaccination from rare clonotypes. These results suggest that de novo acquisition of memory Tfh-like cells upon vaccination may contribute to the longevity of anti-S antibody titers.
摘要：
SARS-CoV-2疫苗已在全球范围内用于抗击COVID-19大流行。为了阐明决定尖峰（S）特异性抗体寿命的因素，我们追踪了BNT162b2疫苗接种前后S特异性T细胞克隆型的特征及其表位和抗S抗体滴度。使用单细胞TCR和RNA测序研究了T细胞受体（TCR）αβ序列和S应答T细胞的mRNA表达。将在用S肽池刺激后高度扩增的199个TCR克隆型重建到报告T细胞系中,用于确定表位和限制性HLA。其中,我们可以确定78个S表位，其中大多数在关注变种（VOCs）中保守。第二次接种疫苗后，在表现出持续抗S抗体滴度的供体中，对回忆S刺激高度响应的T细胞克隆型极化为滤泡辅助性T（Tfh）样细胞（称为“维持者”），但不在“下降者”中。甚至在接种疫苗之前，S反应性CD4+T细胞克隆型确实存在，其中大多数与环境或共生微生物交叉反应。然而,这些克隆型在接种疫苗后收缩。相反，疫苗接种后占主导地位的S反应克隆型在接种前的T细胞池中检测不到，提示通过接种稀有克隆型疫苗建立了高反应性S反应性T细胞.这些结果表明,在疫苗接种后从头获得记忆Tfh样细胞可能有助于抗S抗体滴度的寿命。
