Department of Epidemiology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China.
NHC Key Laboratory of Biosafety, Research Unit of Adaptive Evolution and Control of Emerging Viruses, Chinese Academy of Medical Sciences, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing, 102206, China.
Signal Transduct Target Ther. 2024 Jun 12;9(1):160. doi: 10.1038/s41392-024-01876-3.
The herd immunity against SARS-CoV-2 is continuously consolidated across the world during the ongoing pandemic. However, the potential function of the nonconserved epitopes in the reverse preexisting cross-reactivity induced by SARS-CoV-2 to other human coronaviruses is not well explored. In our research, we assessed T cell responses to both conserved and nonconserved peptides shared by SARS-CoV-2 and SARS-CoV, identifying cross-reactive CD8 T cell epitopes using enzyme-linked immunospot and intracellular cytokine staining assays. Then, in vitro refolding and circular dichroism were performed to evaluate the thermal stability of the HLA/peptide complexes. Lastly, single-cell T cell receptor reservoir was analyzed based on tetramer staining. Here, we discovered that cross-reactive T cells targeting SARS-CoV were present in individuals who had recovered from COVID-19, and identified SARS-CoV-2 CD8 T cell epitopes spanning the major structural antigens. T cell responses induced by the nonconserved peptides between SARS-CoV-2 and SARS-CoV were higher and played a dominant role in the cross-reactivity in COVID-19 convalescents. Cross-T cell reactivity was also observed within the identified series of CD8 T cell epitopes. For representative immunodominant peptide pairs, although the HLA binding capacities for peptides from SARS-CoV-2 and SARS-CoV were similar, the TCR repertoires recognizing these peptides were distinct. Our results could provide beneficial information for the development of peptide-based universal vaccines against coronaviruses.
在当前大流行期间，全球范围内针对 SARS-CoV-2 的群体免疫不断得到巩固。然而，SARS-CoV-2 诱导的针对其他人类冠状病毒的反向预先存在的交叉反应中非保守表位的潜在功能尚未得到充分探索。在我们的研究中，我们评估了针对 SARS-CoV-2 和 SARS-CoV 共有保守和非保守肽的 T 细胞反应，使用酶联免疫斑点和细胞内细胞因子染色测定来鉴定交叉反应性 CD8 T 细胞表位。然后，进行体外重折叠和圆二色性分析，以评估 HLA/肽复合物的热稳定性。最后，基于四聚体染色分析单个细胞 T 细胞受体库。在这里，我们发现针对 SARS-CoV 的交叉反应性 T 细胞存在于从 COVID-19 中康复的个体中，并鉴定了跨越主要结构抗原的 SARS-CoV-2 CD8 T 细胞表位。SARS-CoV-2 和 SARS-CoV 之间非保守肽诱导的 T 细胞反应更高，并在 COVID-19 恢复期患者的交叉反应中起主导作用。在鉴定的一系列 CD8 T 细胞表位内也观察到交叉 T 细胞反应。对于代表性的免疫优势肽对，尽管 SARS-CoV-2 和 SARS-CoV 的肽的 HLA 结合能力相似，但识别这些肽的 TCR 库是不同的。我们的研究结果可为针对冠状病毒的基于肽的通用疫苗的开发提供有益信息。
