Tye Emily X C, Jinks Elizabeth, Haigh Tracey A, Kaul Baksho, Patel Prashant, Parry Helen M, Newby Maddy L, Crispin Max, Kaur Nayandeep, Moss Paul, Drennan Samantha J, Taylor Graham S, Long Heather M
Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
Institute of Cancer and Genomics, University of Birmingham, Birmingham, UK.
Nat Immunol. 2022 Dec;23(12):1726-1734. doi: 10.1038/s41590-022-01351-7. Epub 2022 Dec 1.
CD4 T cells are essential for protection against viruses, including SARS-CoV-2. The sensitivity of CD4 T cells to mutations in SARS-CoV-2 variants of concern (VOCs) is poorly understood. Here, we isolated 159 SARS-CoV-2-specific CD4 T cell clones from healthcare workers previously infected with wild-type SARS-CoV-2 (D614G) and defined 21 epitopes in spike, membrane and nucleoprotein. Lack of CD4 T cell cross-reactivity between SARS-CoV-2 and endemic beta-coronaviruses suggested these responses arose from naïve rather than pre-existing cross-reactive coronavirus-specific T cells. Of the 17 epitopes located in the spike protein, 10 were mutated in VOCs and CD4 T cell clone recognition of 7 of them was impaired, including 3 of the 4 epitopes mutated in omicron. Our results indicated that broad targeting of epitopes by CD4 T cells likely limits evasion by current VOCs. However, continued genomic surveillance is vital to identify new mutations able to evade CD4 T cell immunity.
CD4 T细胞对于抵御包括SARS-CoV-2在内的病毒至关重要。目前对CD4 T细胞对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变异株（VOCs）突变的敏感性了解甚少。在此，我们从先前感染野生型SARS-CoV-2（D614G）的医护人员中分离出159个SARS-CoV-2特异性CD4 T细胞克隆，并在刺突蛋白、膜蛋白和核蛋白中确定了21个表位。SARS-CoV-2与地方性β冠状病毒之间缺乏CD4 T细胞交叉反应性，这表明这些反应源自初始而非预先存在的交叉反应性冠状病毒特异性T细胞。在位于刺突蛋白中的17个表位中，有10个在VOCs中发生了突变，其中7个表位的CD4 T细胞克隆识别能力受损，包括在奥密克戎变异株中发生突变的4个表位中的3个。我们的结果表明，CD4 T细胞对表位的广泛靶向作用可能限制了当前VOCs的逃逸。然而，持续的基因组监测对于识别能够逃避CD4 T细胞免疫的新突变至关重要。
