Institute for Research in Biomedicine, Università della Svizzera italiana, 6500 Bellinzona, Switzerland.
Laboratory of Immunogenetics, Department of Transfusion Medicine and Immuno-Hematology, Fondazione I.R.C.C.S. Policlinico S. Matteo, 27100 Pavia, Italy.
Science. 2021 Jun 18;372(6548):1336-1341. doi: 10.1126/science.abg8985. Epub 2021 May 18.
The identification of CD4 T cell epitopes is instrumental for the design of subunit vaccines for broad protection against coronaviruses. Here, we demonstrate in COVID-19-recovered individuals a robust CD4 T cell response to naturally processed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein and nucleoprotein (N), including effector, helper, and memory T cells. By characterizing 2943 S-reactive T cell clones from 34 individuals, we found that the receptor-binding domain (RBD) is highly immunogenic and that 33% of RBD-reactive clones and 94% of individuals recognized a conserved immunodominant S346-S365 region comprising nested human leukocyte antigen DR (HLA-DR)- and HLA-DP-restricted epitopes. Using pre- and post-COVID-19 samples and S proteins from endemic coronaviruses, we identified cross-reactive T cells targeting multiple S protein sites. The immunodominant and cross-reactive epitopes identified can inform vaccination strategies to counteract emerging SARS-CoV-2 variants.
鉴定 CD4 T 细胞表位对于设计针对冠状病毒的广泛保护的亚单位疫苗至关重要。在这里，我们在 COVID-19 康复个体中证明了对天然加工的严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）刺突（S）蛋白和核蛋白（N）的强大 CD4 T 细胞反应，包括效应器、辅助器和记忆 T 细胞。通过对 34 名个体的 2943 个 S 反应性 T 细胞克隆进行表征，我们发现受体结合域（RBD）具有高度免疫原性，33%的 RBD 反应性克隆和 94%的个体识别包含嵌套人类白细胞抗原 DR（HLA-DR）和 HLA-DP 限制性表位的保守免疫显性 S346-S365 区域。使用 COVID-19 前后的样本和地方性冠状病毒的 S 蛋白，我们鉴定了针对多个 S 蛋白位点的具有交叉反应性的 T 细胞。鉴定的免疫显性和交叉反应性表位可以为对抗新兴 SARS-CoV-2 变体的疫苗接种策略提供信息。
