Institute of Translational Medicine, Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Moscow, Russia.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Front Immunol. 2024 Apr 3;15:1321603. doi: 10.3389/fimmu.2024.1321603. eCollection 2024.
An individual's T-cell repertoire constantly changes under the influence of external and internal factors. Cells that do not receive a stimulatory signal die, while those that encounter and recognize a pathogen or receive a co-stimulatory signal divide, resulting in clonal expansions. T-cell clones can be traced by monitoring the presence of their unique T-cell receptor (TCR) sequence, which is assembled through a process known as V(D)J rearrangement. Tracking T cells can provide valuable insights into the survival of cells after hematopoietic stem cell transplantation (HSCT) or cancer treatment response and can indicate the induction of protective immunity by vaccination. In this study, we report a bioinformatic method for quantifying the T-cell repertoire dynamics from TCR sequencing data. We demonstrate its utility by measuring the T-cell repertoire stability in healthy donors, by quantifying the effect of donor lymphocyte infusion (DLI), and by tracking the fate of the different T-cell subsets in HSCT patients and the expansion of pathogen-specific clones in vaccinated individuals.
个体的 T 细胞 repertoire 在外部和内部因素的影响下不断变化。未接收到刺激信号的细胞死亡，而那些遇到并识别病原体或接收到共刺激信号的细胞则会分裂，导致克隆扩增。可以通过监测其独特的 T 细胞受体（TCR）序列的存在来追踪 T 细胞克隆，该序列通过称为 V(D)J 重排的过程组装而成。跟踪 T 细胞可以深入了解造血干细胞移植（HSCT）或癌症治疗反应后细胞的存活情况，并可以指示疫苗接种诱导的保护性免疫。在这项研究中，我们报告了一种从 TCR 测序数据中定量 T 细胞 repertoire 动态变化的生物信息学方法。我们通过测量健康供体的 T 细胞 repertoire 稳定性、量化供体淋巴细胞输注（DLI）的效果以及跟踪 HSCT 患者不同 T 细胞亚群的命运和接种个体中病原体特异性克隆的扩增，证明了其实用性。
