早期生命印记T细胞克隆大小的层次结构
Early life imprints the hierarchy of T cell clone sizes
摘要：
适应性免疫系统通过选择具有特定受体的细胞克隆来对病原体做出反应。虽然已经详细研究了响应于特定抗原的克隆选择，但尚不清楚一生中暴露于许多抗原如何共同塑造免疫库。在这里，通过T细胞受体测序数据的数学建模和统计分析，我们证明了在围产期时间窗口期间的克隆扩增在人类T细胞库上留下了持久的印记。我们演示了如何经验的缩放法有关的最大的克隆，其大小的排名可以出现在剧目形成克隆生长。我们统计确定早期成立的克隆，并发现它们确实是高度富集的最大的克隆。这种富集甚至在人类衰老数十年后仍然存在，其方式可以通过波动克隆选择模型定量预测。我们的工作提出了一个定量理论的人类T细胞动态兼容的统计规律的剧目组织，并提供了一个机制，早期克隆动态印记的层次结构的T细胞克隆大小与病原体防御和自身免疫的影响。
英文摘要：
The adaptive immune system responds to pathogens by selecting clones of cells with specific receptors. While clonal selection in response to particular antigens has been studied in detail, it is unknown how a lifetime of exposures to many antigens collectively shape the immune repertoire. Here, through mathematical modeling and statistical analyses of T cell receptor sequencing data we demonstrate that clonal expansions during a perinatal time window leave a long-lasting imprint on the human T cell repertoire. We demonstrate how the empirical scaling law relating the rank of the largest clones to their size can emerge from clonal growth during repertoire formation. We statistically identify early founded clones and find that they are indeed highly enriched among the largest clones. This enrichment persists even after decades of human aging, in a way that is quantitatively predicted by a model of fluctuating clonal selection. Our work presents a quantitative theory of human T cell dynamics compatible with the statistical laws of repertoire organization and provides a mechanism for how early clonal dynamics imprint the hierarchy of T cell clone sizes with implications for pathogen defense and autoimmunity.
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