Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
Nuffield Department of Clinical Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
Nat Commun. 2021 Apr 6;12(1):2055. doi: 10.1038/s41467-021-21856-3.
Identification of protective T cell responses against SARS-CoV-2 requires distinguishing people infected with SARS-CoV-2 from those with cross-reactive immunity to other coronaviruses. Here we show a range of T cell assays that differentially capture immune function to characterise SARS-CoV-2 responses. Strong ex vivo ELISpot and proliferation responses to multiple antigens (including M, NP and ORF3) are found in 168 PCR-confirmed SARS-CoV-2 infected volunteers, but are rare in 119 uninfected volunteers. Highly exposed seronegative healthcare workers with recent COVID-19-compatible illness show T cell response patterns characteristic of infection. By contrast, >90% of convalescent or unexposed people show proliferation and cellular lactate responses to spike subunits S1/S2, indicating pre-existing cross-reactive T cell populations. The detection of T cell responses to SARS-CoV-2 is therefore critically dependent on assay and antigen selection. Memory responses to specific non-spike proteins provide a method to distinguish recent infection from pre-existing immunity in exposed populations.
鉴定针对 SARS-CoV-2 的保护性 T 细胞反应需要将感染 SARS-CoV-2 的人与对其他冠状病毒具有交叉反应性免疫的人区分开来。在这里，我们展示了一系列 T 细胞检测方法，这些方法可差异化地捕获免疫功能以表征 SARS-CoV-2 反应。在 168 名经 PCR 确认的 SARS-CoV-2 感染志愿者中发现了针对多种抗原（包括 M、NP 和 ORF3）的强烈体外 ELISpot 和增殖反应，但在 119 名未感染志愿者中很少见。具有近期 COVID-19 相符疾病史的高暴露血清阴性医护人员表现出感染特征的 T 细胞反应模式。相比之下，>90%的康复期或未暴露者对刺突亚单位 S1/S2 表现出增殖和细胞乳酸反应，表明存在预先存在的交叉反应性 T 细胞群体。因此，T 细胞对 SARS-CoV-2 的检测在很大程度上取决于检测方法和抗原选择。针对特定非刺突蛋白的记忆反应提供了一种方法，可以在暴露人群中区分近期感染和预先存在的免疫。
