As the establishment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell memory in children remains largely unexplored, we recruited convalescent COVID-19 children and adults to define their circulating memory SARS-CoV-2-specific CD4⁺ and CD8⁺ T cells prior to vaccination. We analyzed epitope-specific T cells directly ex vivo using seven HLA class I and class II tetramers presenting SARS-CoV-2 epitopes, together with Spike-specific B cells. Unvaccinated children who seroconverted had comparable Spike-specific but lower ORF1a- and N-specific memory T cell responses compared with adults. This agreed with our TCR sequencing data showing reduced clonal expansion in children. A strong stem cell memory phenotype and common T cell receptor motifs were detected within tetramer-specific T cells in seroconverted children. Conversely, children who did not seroconvert had tetramer-specific T cells of predominantly naive phenotypes and diverse TCRαβ repertoires. Our study demonstrates the generation of SARS-CoV-2-specific T cell memory with common TCRαβ motifs in unvaccinated seroconverted children after their first virus encounter.

由于严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 特异性 T 细胞记忆在儿童中的建立在很大程度上仍未得到探索，我们招募了康复期 COVID-19 儿童和成人来确定他们的循环记忆 SARS-CoV-2 特异性 CD4 ⁺和 CD8 ⁺ T 细胞接种疫苗前。我们直接离体分析了表位特异性 T 细胞使用七个 HLA I 类和 II 类四聚体呈现 SARS-CoV-2 表位，以及刺突特异性 B 细胞。与成人相比，血清转化的未接种疫苗的儿童具有相当的刺突特异性但较低的 ORF1a 和 N 特异性记忆 T 细胞反应。这与我们的 TCR 测序数据一致，显示儿童的克隆扩增减少。在血清转化儿童的四聚体特异性 T 细胞中检测到强烈的干细胞记忆表型和常见的 T 细胞受体基序。相反，未发生血清转化的儿童具有四聚体特异性 T 细胞，其主要是幼稚表型和多种 TCRαβ 库。我们的研究表明，未接种疫苗的血清转化儿童在首次接触病毒后会产生具有共同 TCRαβ 基序的 SARS-CoV-2 特异性 T 细胞记忆。