Identification of HLA-A2 restricted CD8+ T cell epitopes in SARS-CoV-2 structural proteins,Journal of Leukocyte Biology

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Identification of HLA-A2 restricted CD8+ T cell epitopes in SARS-CoV-2 structural proteins
Journal of Leukocyte Biology ( IF 3.6 ) Pub Date : 2021-07-07 , DOI: 10.1002/jlb.4ma0621-020r
Jieping Deng _{1,

2} , Junping Pan _{1,

2} , Minghui Qiu _{1,

2} , Lipeng Mao _{1,

2} , Zhigang Wang ₃ , Guodong Zhu _{2,

4} , Lijuan Gao _{1,

2} , Jun Su ₃ , Yutian Hu ₅ , Oscar Junhong Luo _{2,

6} , Guobing Chen _{1,

2} , Pengcheng Wang _{1,

2}

Affiliation

The outbreak of coronavirus disease 2019 (COVID-19) has now become a pandemic, and the etiologic agent is the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). T cell mediated immune responses play an important role in virus controlling; however, the understanding of the viral protein immunogenicity and the mechanisms of the induced responses are still limited. So, identification of specific epitopes and exploring their immunogenic properties would provide valuable information. In our study, we utilized the Immune Epitope Database and Analysis Resource and NetMHCpan to predict HLA-A2 restricted CD8⁺ T cell epitopes in structural proteins of SARS-CoV-2, and screened out 23 potential epitopes. Among them, 18 peptides showed strong or moderate binding with HLA-A2 with a T2A2 cell binding model. Next, the mixed peptides induced the increased expression of CD69 and highly expressed levels of IFN-γ and granzyme B in CD8⁺ T cells, indicating effective activation of specific CD8⁺ T cells. In addition, the peptide-activated CD8⁺ T cells showed significantly increased killing to the target cells. Furthermore, tetramer staining revealed that the activated CD8⁺ T cells mainly recognized seven epitopes. All together, we identified specific CD8⁺ T cell epitopes in SARS-CoV-2 structural proteins, which could induce the production of specific immune competent CD8⁺ T cells. Our work contributes to the understanding of specific immune responses and vaccine development for SARS-CoV-2.

中文翻译：

SARS-CoV-2 结构蛋白中 HLA-A2 限制性 CD8+ T 细胞表位的鉴定

2019 年冠状病毒病 (COVID-19) 的爆发现已成为大流行病，病原体是严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2)。T 细胞介导的免疫反应在病毒控制中发挥重要作用；然而，对病毒蛋白免疫原性和诱导反应机制的了解仍然有限。因此，鉴定特定表位并探索其免疫原性将提供有价值的信息。在我们的研究中，我们利用免疫表位数据库和分析资源以及 NetMHCpan 来预测 HLA-A2 限制性 CD8 ⁺SARS-CoV-2结构蛋白中的T细胞表位，筛选出23个潜在表位。其中，18 种肽在 T2A2 细胞结合模型中显示出与 HLA-A2 的强或中度结合。^{接下来，混合肽诱导 CD8 +} T 细胞中 CD69 的表达增加以及 IFN-γ 和颗粒酶 B 的高表达水平，表明特定 CD8 ⁺ T 细胞的有效激活。此外，肽激活的 CD8 ⁺ T 细胞对靶细胞的杀伤力显着增加。此外，四聚体染色显示活化的 CD8 ⁺ T 细胞主要识别七个表位。总之，我们确定了特定的 CD8 ⁺SARS-CoV-2 结构蛋白中的 T 细胞表位，可诱导产生特异性免疫活性 CD8 ⁺ T 细胞。我们的工作有助于了解 SARS-CoV-2 的特异性免疫反应和疫苗开发。

更新日期：2021-07-07

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