对疫苗应答T细胞克隆的精确跟踪揭示了同卵双胞胎的趋同和个性化反应
Precise tracking of vaccine-responding T-cell clones reveals convergent and personalized response in identical twins
摘要：
T细胞受体（TCR）库数据包含有关感染的信息，可用于疾病诊断和疫苗开发，但提取这些信息仍然是一个重大挑战。在这里，我们开发了一个统计框架来检测TCR克隆增殖和收缩的纵向剧目数据。我们将这一框架应用于三对接种黄热病疫苗的同卵双胞胎的数据。我们在每个供体中鉴定了500-1500个应答TCR，并使用三种独立的测定法对其进行了验证。虽然响应TCR大多是私人的，尽管双胞胎之间有较高的重叠，但可以使用基于序列相似性的分类器很好地预测它们。我们的方法也可以应用于感染后获得的样品，使其适合在临床上系统发现新的感染特异性TCR。
英文摘要：
T-cell receptor (TCR) repertoire data contain information about infections that could be used in disease diagnostics and vaccine development, but extracting that information remains a major challenge. Here we developed a statistical framework to detect TCR clone proliferation and contraction from longitudinal repertoire data. We applied this framework to data from three pairs of identical twins immunized with the yellow fever vaccine. We identified 500-1500 responding TCRs in each donor and validated them using three independent assays. While the responding TCRs were mostly private, albeit with higher overlap between twins, they could be well predicted using a classifier based on sequence similarity. Our method can also be applied to samples obtained post-infection, making it suitable for systematic discovery of new infection-specific TCRs in the clinic.
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