BACKGROUND The adaptive immune system maintains a diversity of T cells capable of recognizing a broad array of antigens. Each T cell's specificity for antigens is determined by its T cell receptors (TCRs), which together across all T cells form a repertoire of millions of unique receptors in each individual. Although many studies have examined how TCR repertoires change in response to disease or drugs, few have explored the temporal dynamics of the TCR repertoire in healthy individuals. RESULTS Here we report immunosequencing of TCR β chains (TCRβ) from the blood of three healthy individuals at eight time points over one year. TCRβ repertoires of all peripheral-blood T cells and sorted memory T cells clustered clearly by individual, systematically demonstrating that TCRβ repertoires are specific to individuals across time. This individuality was absent from TCRβs from naive T cells, suggesting that the differences resulted from an individual's antigen exposure history, not genetic background. Many characteristics of the TCRβ repertoire (e.g., diversity, clonality) were stable across time, although we found evidence of T cell expansion dynamics even within healthy individuals. We further identified a subset of "persistent" TCRβs present across all time points. These receptors were rich in clonal and highly public receptors and may play a key role in immune system maintenance. CONCLUSIONS Our results highlight the importance of longitudinal sampling of the immune system, providing a much-needed baseline for TCRβ dynamics in healthy individuals. Such a baseline will improve interpretation of changes in the TCRβ repertoire during disease or treatment.

中文翻译：

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健康人的纵向免疫测序揭示了富含高度公开受体的持久性T细胞受体。

背景技术适应性免疫系统维持能够识别多种抗原的多种T细胞。每个T细胞对抗原的特异性由其T细胞受体（TCR）决定，它们跨所有T细胞共同构成每个个体中数百万个独特受体的库。尽管许多研究检查了TCR记忆库如何响应疾病或药物而变化，但很少有研究探讨健康个体中TCR记忆库的时间动态。结果在这里，我们报告了在一年中的八个时间点从三个健康个体的血液中获得的TCRβ链（TCRβ）的免疫测序。所有外周血T细胞和分类记忆T细胞的TCRβ组成被个体清楚地聚类，系统地证明了TCRβ组成对于时间跨度是特定于个体的。原始T细胞的TCRβ不存在这种个性，这表明差异是由于个体的抗原暴露史而不是遗传背景引起的。尽管我们发现即使在健康个体中也存在T细胞扩张动态的证据，但TCRβ曲目的许多特征（例如多样性，克隆性）在整个时间都是稳定的。我们进一步确定了在所有时间点都存在的“持久性”TCRβ的子集。这些受体富含克隆和高度公开的受体，可能在免疫系统维持中起关键作用。结论我们的结果突出了免疫系统纵向采样的重要性，为健康个体中TCRβ动力学提供了急需的基线。这样的基线将改善对疾病或治疗期间TCRβ组成变化的解释。