Zhang Jie, Lu Dan, Li Min, Liu Maoshun, Yao Sijia, Zhan Jianbo, Liu William J, Gao George F
NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.
China CDC Wkly. 2022 Feb 4;4(5):83-87. doi: 10.46234/ccdcw2021.258.
Similar to antibody detection, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-specific T-cell response evaluation is also pivotal among the coronavirus disease 2019 (COVID-19) convalescents and the vaccinated populations. Nucleocapsid (N) protein is one of the main structural proteins of SARS-CoV-2 and can trigger T-cell responses in humans.
An overlapping peptide pool covering the full length of the N protein was designed, peptides with positive T-cell activating potency in COVID-19 convalescents were screened, and CD8 T cell epitopes were further identified. The epitope was used to detect the SARS-CoV-2-specific CD8 T cell responses in COVID-19 convalescents based in intracellular cytokine staining and tetramer staining in flow cytometry.
A human leukocyte antigen A (HLA-A)1101-restricted CD8 T cell epitope, which could stimulate the production of IFN-γ via peripheral blood mononuclear cells (PBMCs) of the convalescents was defined, and the tetramer generated with this epitope could detect SARS-CoV-2-specific T cells in the PBMCs of the convalescents. The structural investigation eliminated that the epitope was a typical HLA-A1101-restricted T-cell epitope which was conserved among all the sarbecoviruses.
The newly identified SARS-CoV-2-derived T-cell epitope was helpful to detect the cellular immunity against different sarbecoviruses including SARS-CoV and SARS-CoV-2. This study provided an evaluation method and also a peptide candidate for the research and development of T-cell based vaccine for the virus.
与抗体检测类似，严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）特异性T细胞反应评估在2019冠状病毒病（COVID-19）康复者和接种疫苗人群中也至关重要。核衣壳（N）蛋白是SARS-CoV-2的主要结构蛋白之一，可在人类中引发T细胞反应。
设计覆盖N蛋白全长的重叠肽库，筛选在COVID-19康复者中具有阳性T细胞激活效力的肽，并进一步鉴定CD8 T细胞表位。基于流式细胞术中的细胞内细胞因子染色和四聚体染色，用该表位检测COVID-19康复者中SARS-CoV-2特异性CD8 T细胞反应。
确定了一种人类白细胞抗原A（HLA-A）1101限制性CD8 T细胞表位，其可通过康复者的外周血单核细胞（PBMC）刺激产生γ干扰素，并且用该表位产生的四聚体可检测康复者PBMC中的SARS-CoV-2特异性T细胞。结构研究排除了该表位是所有沙贝病毒中保守的典型HLA-A1101限制性T细胞表位。
新鉴定的源自SARS-CoV-2的T细胞表位有助于检测针对包括SARS-CoV和SARS-CoV-2在内的不同沙贝病毒的细胞免疫。本研究为该病毒基于T细胞的疫苗研发提供了一种评估方法和一个肽候选物。
