Dynamics of TCR ß repertoires from serial sampling of healthy individuals
Dynamics of TCR ß repertoires from serial sampling of healthy individuals
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TCR 动态 - 来自健康个体连续采样的所有内容
DOI：
10.1101/2022.05.11.491566
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Ayestaran I
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文献类型：
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作者：
Ayestaran I
T 细胞受体 (TCR) 库提供抗原暴露的历史记录。然而，健康个体中 TCR 的动态变化在很大程度上仍然未知。健康个体中有多少是处于免疫选择之下的？由于收敛特异性，免疫选择下的序列组是否具有相似的动态？ TCR的动态相似性和序列相似性之间有什么关系？在这里，我们开发了一个统计框架，用于识别时间序列库数据中免疫选择下的克隆型。将此框架应用于一年内从 3 名健康志愿者收集的连续采样库中，我们能够检测到数百个正在进行强免疫选择的 TCR，其中克隆型频率可以在短短一个月的时间内发生数量级的变化。免疫选择下的克隆型属于少数不同的动态簇，每个簇都表现出高度协调的时间行为，表明存在共同的免疫原性刺激。虽然动态簇内的克隆型子集显示出共享的氨基酸基序使用，但大多数克隆型却没有，这表明相同的免疫原性刺激会引发不同的 TCR 反应。相反，仅使用共享氨基酸基序在免疫选择下识别出的克隆型要少得多，并且这些克隆型通常不会表现出相关的时间行为。这些结果凸显了利用 TCR 库动态中包含的信息以与序列无关的方式识别对相同免疫原性刺激做出反应的克隆型的潜力。
T-cell receptor (TCR) repertoires provide a historical record of antigen exposure. However, the dynamics of TCR repertoires in healthy individuals remain largely uncharacterised. How much of the repertoire is under immune selection in healthy individuals? Do groups of sequences under immune selection share similar dynamics due to convergent specificity? What is the relationship between dynamic similarity and sequence similarity of TCRs? Here we develop a statistical framework for identifying clonotypes under immune selection in time series repertoire data. Applying this framework to serially sampled repertoires collected over the course of a year from 3 healthy volunteers, we are able to detect hundreds of TCRs undergoing strong immune selection whereby clonotype frequencies can change by orders of magnitude over timescales as short as a month. Clonotypes under immune selection belong to a handful of distinct dynamic clusters each of which show highly coordinated temporal behaviour suggesting a common immunogenic stimulus. Whilst a subset of clonotypes within dynamic clusters show shared amino acid motif usage, most do not, suggesting the same immunogenic stimulus elicits a diverse TCR response. Conversely, shared amino acid motif usage alone identifies far fewer clonotypes under immune selection and these clonotypes do not routinely exhibit correlated temporal behaviour. These results highlight the potential of using information contained in thedynamicsof TCR repertoires for identifying clonotypes responding to the same immunogenic stimulus in a sequence agnostic way.