Zhao Yu, Peng Min, He Chengtao, Li Min, Han Xuelian, Fu Qiang, Wu Yandan, Yue Fangping, Yan Chunguang, Zhao Guangyu, Shen Chuanlai
Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, China.
Blood Group Reference Laboratory, Nanjing Red Cross Blood Center, Nanjing, China.
Front Immunol. 2025 May 21;16:1545510. doi: 10.3389/fimmu.2025.1545510. eCollection 2025.
Since the outbreak of novel coronavirus pneumonia (COVID-19), numerous T-cell epitopes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteome have been reported. However, most of the identified CD8 T-cell epitopes have been restricted primarily by HLA-A allotypes. The epitopes restricted by HLA-B and HLA-C allotypes are limited. This study focuses on the screening of T-cell epitopes restricted by 13 prevalent HLA-B and 13 prevalent HLA-C allotypes, which cover over 70% and 90% of the Chinese and Northeast Asian populations, respectively. Totally, 67 HLA-B restricted and 53 HLA-C restricted epitopes were validated as immunogenic epitopes with a herd predominance rate by peptide-PBMCs coculture experiments using the PBMCs from convalescent Chinese cohort. In addition, 26 transfected cell lines expressing indicated HLA-B or HLA-C allotype were established, and used in the competitive peptide binding assays to define the affinities and cross-restriction of each validated epitope binding to HLA-B or HLA-C allotypes. These data will facilitate the design of T-cell-directed vaccines and SARS-CoV-2-specific T-cell detection tools tailored to the Northeast Asian population. The herd test of functionally validated T-cell epitopes, and the competitive peptide binding assay onto cell line array expressing prevalent HLA allotypes may serve as an additional criterion for selecting T-cell epitopes used in vaccine.
自新型冠状病毒肺炎(COVID-19)疫情爆发以来,严重急性呼吸综合征冠状病毒2(SARS-CoV-2)蛋白质组中的众多T细胞表位已被报道。然而,大多数已鉴定的CD8 T细胞表位主要受HLA-A同种异型限制。受HLA-B和HLA-C同种异型限制的表位有限。本研究聚焦于筛选受13种常见HLA-B和13种常见HLA-C同种异型限制的T细胞表位,这些同种异型分别覆盖了超过70%的中国人群和90%的东北亚人群。通过使用来自中国康复者队列的外周血单个核细胞(PBMC)进行肽 - PBMC共培养实验,总共67个受HLA-B限制的表位和53个受HLA-C限制的表位被验证为具有群体优势率的免疫原性表位。此外,建立了26个表达指定HLA-B或HLA-C同种异型的转染细胞系,并用于竞争性肽结合测定,以确定每个验证表位与HLA-B或HLA-C同种异型结合的亲和力和交叉限制性。这些数据将有助于设计针对东北亚人群的T细胞导向疫苗和SARS-CoV-2特异性T细胞检测工具。对功能验证的T细胞表位进行群体测试,以及在表达常见HLA同种异型的细胞系阵列上进行竞争性肽结合测定,可作为选择用于疫苗的T细胞表位的额外标准。