Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva University Hospitals, Geneva, Switzerland.
CANSEARCH Research Platform for Pediatric Oncology and Hematology, Faculty of Medicine, Department of Pediatrics, Gynecology and Obstetrics, University of Geneva, Geneva, Switzerland.
HLA. 2023 Dec;102(6):720-730. doi: 10.1111/tan.15158. Epub 2023 Jul 18.
HLA antigen presentation and T-cell mediated immunity are critical to control acute viral infection such as COVID-19 caused by SARS-CoV-2. Recent data suggest that both the depth of peptide presentation and the breadth of the T-cell repertoire are associated with disease outcome. It has also been shown that unexposed subjects can develop strong T-cell responses against SARS-CoV-2 due to heterologous immunity. In this study, we explored the anti-SARS-CoV-2 T-cell repertoire by analyzing previously published T-cell receptor (TCR) CDR3β immunosequencing data in a cohort of 116 healthy donors and in the context of immune reconstitution after allogeneic hematopoietic stem cell transplantation in 116 recipients collected during the pre-COVID-19 era. For this, 143,310 publicly available SARS-CoV-2 specific T-cell sequences were investigated among the 3.5 million clonotypes in the cohort. We also performed HLA class I peptide binding predictions using the reference proteome of the virus and high resolution genotyping data in these patients. We could demonstrate that individuals are fully equipped at the genetic level to recognize SARS-CoV-2. This is evidenced by the 5% median cumulative frequency of clonotypes having their sequence matched to a SARS-CoV-2 specific T-cell. In addition, any combination of HLA class I variants in this cohort is associated with a broad capacity of presenting hundreds of SARS-CoV-2 derived peptides. These results could be explained by heterologous immunity and random somatic TCR recombination. We speculate that these observations could explain the efficacy of the specific immune response against SARS-CoV-2 in individuals without risk factors of immunodeficiency and infected prior to vaccination.
HLA 抗原呈递和 T 细胞介导的免疫对于控制急性病毒感染至关重要，例如由 SARS-CoV-2 引起的 COVID-19。最近的数据表明，肽呈递的深度和 T 细胞库的广度都与疾病结局相关。此外，还表明未暴露的受试者由于异源免疫可以针对 SARS-CoV-2 产生强烈的 T 细胞反应。在这项研究中，我们通过分析之前发表的 116 名健康供体队列中的 T 细胞受体（TCR）CDR3β 免疫测序数据，并结合在 COVID-19 之前的同种异体造血干细胞移植接受者队列中进行的免疫重建，探索了抗 SARS-CoV-2 的 T 细胞库。为此，在队列的 350 万个克隆型中，研究了 143310 个公开可用的 SARS-CoV-2 特异性 T 细胞序列。我们还使用病毒的参考蛋白质组和这些患者中的高分辨率基因分型数据进行了 HLA Ⅰ类肽结合预测。我们能够证明个体在遗传水平上完全具备识别 SARS-CoV-2 的能力。这可以通过 5%的中位数累积频率来证明，即具有其序列与 SARS-CoV-2 特异性 T 细胞匹配的克隆型的频率。此外，该队列中任何 HLA Ⅰ类变体的组合都与呈现数百种源自 SARS-CoV-2 的肽的广泛能力相关。这些结果可以通过异源免疫和随机体细胞 TCR 重组来解释。我们推测，这些观察结果可以解释在没有免疫缺陷风险因素且在接种疫苗之前感染的个体中针对 SARS-CoV-2 的特异性免疫反应的有效性。
