新型冠状病毒抗原表位及其特异性T细胞的筛选  

The Screening of SARS-CoV-2 Epitopes and Their Specific T Cells

作　　者：戴春烨 许雯珏 刘凌峰 DAI Chunye;XU Wenjue;LIU Lingfeng(School of Life Sciences,Fudan University,Shanghai 200438,China)

机构地区：[1]复旦大学生命科学学院,上海200438

出　　处：《中国细胞生物学学报》2022年第7期1238-1247,共10页Chinese Journal of Cell Biology

基　　金：国家自然科学基金面上项目(批准号:KRH1322722)资助的课题。

摘　　要：该文利用MHC四聚体技术从接种新冠疫苗人群体内筛选出SARS-CoV-2特异性T细胞。该实验针对中国人群最为常见的HLA-A*0201分型,通过IEDB、SYFPEITHI和NetMHCpan4.0等生物信息学方法预测新冠病毒S蛋白抗原肽,并结合UV-置换抗原肽实验验证,确定了7个9肽抗原肽,分别是S538、S976、S996、S1060、S1185、S1192和S1220,其中S1220的亲和性最高,S538的亲和性最低。接着利用MHC四聚体技术合成了除S538外的6种HLA-A*0201限制性S蛋白特异性四聚体,并在接种疫苗的HLA-A*0201人群PBMCs中筛出了其特异性的T细胞。这证明了接种新冠疫苗的HLA-A*0201人群体内的确存在针对SARS-CoV-2的细胞免疫反应,同时发现不同个体对SARS-CoV-2不同抗原肽免疫反应产生的特异性T细胞在数量和频率上存在差异性,为后续研究新冠疫苗引起的细胞免疫作了铺垫。In this study,SARS-CoV-2-specific T cells were screened from COVID-19 vaccinated humans by MHC tetramer technology.In this experiment,aiming at the most common HLA-A*0201 typing in the Chinese population,seven SARS-CoV-2 spike antigen peptides were identified through the prediction of bioinformatics methods such as IEDB,SYFPEITHI and NetMHCpan4.0 combined with the experimental test of UV-substituted antigenic peptides.The 9-peptide antigenic peptides of the protein are S538,S976,S996,S1060,S1185,S1192 and S1220,of which S1220 has the highest affinity and S538 has the lowest affinity.Six HLA-A*0201-restricted S protein-specific tetramers except S538 were synthesized by MHC tetramer technology,and their specific T tetramers were screened in vaccinated HLA-A*0201 population PBMCs cell.It is proved that there is indeed a cellular immune response against SARS-CoV-2 in the HLA-A*0201 population vaccinated against SARS-CoV-2.At the same time,it is found that the specific T cells produced by different individuals in the immune response to different antigenic peptides of SARS-CoV-2 vary in number and size.There are differences in frequency,paving the way for subsequent research on cellular immunity caused by the new crown vaccine.

关 键 词：SARS-CoV-2 S蛋白 抗原肽 MHC四聚体 T细胞 

分 类 号：R392[医药卫生—免疫学]