A central feature of the SARS-CoV-2 pandemic is that some individuals become severely ill or die, whereas others have only a mild disease course or are asymptomatic. Here we report development of an improved multimeric αβ T cell staining reagent platform, with each maxi-ferritin “spheromer” displaying 12 peptide-MHC complexes. Spheromers stain specific T cells more efficiently than peptide-MHC tetramers and capture a broader portion of the sequence repertoire for a given peptide-MHC. Analyzing the response in unexposed individuals, we find that T cells recognizing peptides conserved amongst coronaviruses are more abundant and tend to have a “memory” phenotype, compared to those unique to SARS-CoV-2. Significantly, CD8⁺ T cells with these conserved specificities are much more abundant in COVID-19 patients with mild disease versus those with a more severe illness, suggesting a protective role.

SARS-CoV-2 大流行的一个核心特征是，一些人病情严重或死亡，而另一些人的病程较轻或无症状。在这里，我们报告了改进的多聚 αβ T 细胞染色试剂平台的开发，每个 maxi-ferritin“spheromer” 显示 12 个肽-MHC 复合物。球体比肽-MHC 四聚体更有效地对特定 T 细胞进行染色，并捕获给定肽-MHC 序列库的更广泛部分。通过分析未接触过的个体的反应，我们发现与 SARS-CoV-2 特有的相比，识别冠状病毒中保守肽的 T 细胞更加丰富，并且往往具有“记忆”表型。值得注意的是，具有这些保守特异性的 CD8 ⁺ T 细胞在患有轻度疾病的 COVID-19 患者中比患有更严重疾病的患者中更加丰富，这表明具有保护作用。