Both B cells and T cells are involved in an effective immune response to SARS-CoV-2, the disease-causing virus of COVID-19. While B cells—with the indispensable help of CD4⁺ T cells—are essential to generate neutralizing antibodies, T cells on their own have been recognized as another major player in effective anti-SARS-CoV-2 immunity. In this report, we provide insights into the characteristics of individual HLA-A*02:01- and HLA-A*24:02-restricted SARS-CoV-2-reactive TCRs, isolated from convalescent COVID-19 patients. We observed that SARS-CoV-2-reactive T-cell populations were clearly detectable in convalescent samples and that TCRs isolated from these T cell clones were highly functional upon ectopic re-expression. The SARS-CoV-2-reactive TCRs described in this report mediated potent TCR signaling in reporter assays with low nanomolar EC50 values. We further demonstrate that these SARS-CoV-2-reactive TCRs conferred powerful T-cell effector function to primary CD8⁺ T cells as evident by a robust anti-SARS-CoV-2 IFN-γ response and in vitro cytotoxicity. We also provide an example of a long-lasting anti-SARS-CoV-2 memory response by reisolation of one of the retrieved TCRs 5 months after initial sampling. Taken together, these findings contribute to a better understanding of anti-SARS-CoV-2 T-cell immunity and may contribute to paving the way toward immunotherapeutics approaches targeting SARS-CoV-2.

中文翻译：

---

从恢复期 COVID-19 患者中分离出的 SARS-CoV-2 反应性 T 细胞受体赋予有效的 T 细胞效应功能

B 细胞和 T 细胞都参与对 SARS-CoV-2（COVID-19 的致病病毒）的有效免疫反应。^{虽然 B 细胞（在 CD4 +} T 细胞的不可或缺的帮助下）对于产生中和抗体至关重要，但 T 细胞本身已被认为是有效抗 SARS-CoV-2 免疫的另一个主要参与者。在本报告中，我们深入了解从恢复期 COVID-19 患者中分离出的 HLA-A*02:01 和 HLA-A*24:02 限制性 SARS-CoV-2 反应性 TCR 的特征。我们观察到，在恢复期样本中可以清楚地检测到 SARS-CoV-2 反应性 T 细胞群，并且从这些 T 细胞克隆中分离出的 TCR 在异位重新表达后具有高度功能。本报告中描述的 SARS-CoV-2 反应性 TCR 在报告基因检测中以低纳摩尔 EC50 值介导有效的 TCR 信号传导。^{我们进一步证明，这些 SARS-CoV-2 反应性 TCR 赋予原代 CD8 +} T 细胞强大的 T 细胞效应功能，这一点可以通过强大的抗 SARS-CoV-2 IFN-γ 反应和体外细胞毒性来证明。我们还提供了一个持久的抗 SARS-CoV-2 记忆反应的例子，通过在初次采样 5 个月后重新分离检索到的 TCR 之一来实现。总而言之，这些发现有助于更好地了解抗 SARS-CoV-2 T 细胞免疫，并可能有助于为针对 SARS-CoV-2 的免疫治疗方法铺平道路。