MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
Nat Immunol. 2020 Nov;21(11):1336-1345. doi: 10.1038/s41590-020-0782-6. Epub 2020 Sep 4.
The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, using interferon-γ-based assays with peptides spanning SARS-CoV-2 except ORF1. The breadth and magnitude of T cell responses were significantly higher in severe as compared with mild cases. Total and spike-specific T cell responses correlated with spike-specific antibody responses. We identified 41 peptides containing CD4 and/or CD8 epitopes, including six immunodominant regions. Six optimized CD8 epitopes were defined, with peptide-MHC pentamer-positive cells displaying the central and effector memory phenotype. In mild cases, higher proportions of SARS-CoV-2-specific CD8 T cells were observed. The identification of T cell responses associated with milder disease will support an understanding of protective immunity and highlights the potential of including non-spike proteins within future COVID-19 vaccine design.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）疫苗和疗法的发展将取决于对病毒免疫的理解。我们使用基于干扰素-γ的检测方法，用跨越 SARS-CoV-2 的肽段（除 ORF1 外）研究了 42 名从 COVID-19 中康复的患者（28 名轻症和 14 名重症）和 16 名未暴露的供体的 T 细胞记忆。与轻症相比，重症患者的 T 细胞反应的广度和幅度显著更高。总 T 细胞和刺突蛋白特异性 T 细胞反应与刺突蛋白特异性抗体反应相关。我们鉴定出 41 个包含 CD4 和/或 CD8 表位的肽段，包括 6 个免疫优势区。定义了 6 个优化的 CD8 表位，其肽-MHC 五聚体阳性细胞显示中央和效应记忆表型。在轻症病例中，观察到更多的 SARS-CoV-2 特异性 CD8 T 细胞。与轻症疾病相关的 T 细胞反应的鉴定将有助于理解保护性免疫，并强调在未来 COVID-19 疫苗设计中纳入非刺突蛋白的潜力。
