The functional relevance of pre-existing cross-immunity to SARS-CoV-2 is a subject of intense debate. Here, we show that human endemic coronavirus (HCoV)-reactive and SARS-CoV-2-cross-reactive CD4⁺ T cells are ubiquitous but decrease with age. We identified a universal immunodominant coronavirus-specific spike peptide (S816-830) and demonstrate that pre-existing spike- and S816-830-reactive T cells were recruited into immune responses to SARS-CoV-2 infection and their frequency correlated with anti-SARS-CoV-2-S1-IgG antibodies. Spike-cross-reactive T cells were also activated after primary BNT162b2 COVID-19 mRNA vaccination displaying kinetics similar to secondary immune responses. Our results highlight the functional contribution of pre-existing spike-cross-reactive T cells in SARS-CoV-2 infection and vaccination. Cross-reactive immunity may account for the unexpectedly rapid induction of immunity following primary SARS-CoV-2 immunization and the high rate of asymptomatic/mild COVID-19 disease courses.

中文翻译：

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交叉反应性 CD4+ T 细胞在感染和接种疫苗后增强 SARS-CoV-2 免疫反应

预先存在的交叉免疫与 SARS-CoV-2 的功能相关性是一个激烈争论的主题。在这里，我们显示人类地方性冠状病毒 (HCoV) 反应性和 SARS-CoV-2 交叉反应性 CD4 ⁺T 细胞无处不在，但随着年龄的增长而减少。我们鉴定了一种普遍的免疫显性冠状病毒特异性刺突肽 (S816-830)，并证明预先存在的刺突反应和 S816-830 反应性 T 细胞被募集到对 SARS-CoV-2 感染的免疫反应中，并且它们的频率与抗- SARS-CoV-2-S1-IgG 抗体。在初次 BNT162b2 COVID-19 mRNA 疫苗接种后，刺突交叉反应性 T 细胞也被激活，显示出类似于二次免疫反应的动力学。我们的结果强调了预先存在的刺突交叉反应性 T 细胞在 SARS-CoV-2 感染和疫苗接种中的功能贡献。交叉反应免疫可能是 SARS-CoV-2 初次免疫后意外快速诱导免疫以及无症状/轻度 COVID-19 病程发生率高的原因。