Repertoire Immune Medicines, Cambridge, MA, USA.
Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Sci Immunol. 2022 Jan 21;7(67):eabk3070. doi: 10.1126/sciimmunol.abk3070.
Effective presentation of antigens by human leukocyte antigen (HLA) class I molecules to CD8 T cells is required for viral elimination and generation of long-term immunological memory. In this study, we applied a single-cell, multiomic technology to generate a unified ex vivo characterization of the CD8 T cell response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across four major HLA class I alleles. We found that HLA genotype conditions key features of epitope specificity, TCRα/β sequence diversity, and the utilization of pre-existing SARS-CoV-2-reactive memory T cell pools. Single-cell transcriptomics revealed functionally diverse T cell phenotypes of SARS-CoV-2-reactive T cells, associated with both disease stage and epitope specificity. Our results show that HLA variations notably influence the CD8 T cell repertoire shape and utilization of immune recall upon SARS-CoV-2 infection.
人类白细胞抗原 (HLA) Ⅰ类分子有效呈递抗原是清除病毒和产生长期免疫记忆所必需的。在这项研究中，我们应用单细胞多组学技术，对四种主要 HLA Ⅰ类等位基因中对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的 CD8 T 细胞反应进行了统一的体外特征描述。我们发现，HLA 基因型决定了表位特异性、TCRα/β 序列多样性以及利用预先存在的 SARS-CoV-2 反应性记忆 T 细胞库的关键特征。单细胞转录组学揭示了 SARS-CoV-2 反应性 T 细胞的功能多样的表型，与疾病阶段和表位特异性相关。我们的结果表明，HLA 变异显著影响 CD8 T 细胞库的形成以及 SARS-CoV-2 感染后的免疫记忆利用。
