Detecting T-cell clonal expansions and quantifying clone survival using deep profiling of immune repertoires

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...

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Main Authors: Anastasia V. Pavlova, Ivan V. Zvyagin, Mikhail Shugay
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-04-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1321603/full
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author Anastasia V. Pavlova
Anastasia V. Pavlova
Ivan V. Zvyagin
Ivan V. Zvyagin
Ivan V. Zvyagin
Mikhail Shugay
Mikhail Shugay
author_facet Anastasia V. Pavlova
Anastasia V. Pavlova
Ivan V. Zvyagin
Ivan V. Zvyagin
Ivan V. Zvyagin
Mikhail Shugay
Mikhail Shugay
author_sort Anastasia V. Pavlova
collection DOAJ
description 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 de novo 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.
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spelling doaj.art-af5032eadcf744bdb530be0a40851f292024-04-03T04:35:31ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-04-011510.3389/fimmu.2024.13216031321603Detecting T-cell clonal expansions and quantifying clone survival using deep profiling of immune repertoiresAnastasia V. Pavlova0Anastasia V. Pavlova1Ivan V. Zvyagin2Ivan V. Zvyagin3Ivan V. Zvyagin4Mikhail Shugay5Mikhail Shugay6Institute of Translational Medicine, Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, RussiaInstitute of Translational Medicine, Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, RussiaDmitriy Rogachev National Center of Pediatric Hematology, Oncology and Immunology, Moscow, RussiaInstitute of Translational Medicine, Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, RussiaAn 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 de novo 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.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1321603/fullT cell repertoire analysisadaptive immune receptor repertoire (AIRR)T cell receptor (TCR)clonal trackinghematopoietic (stem) cell transplantation (HCST)immune reconstitution
spellingShingle Anastasia V. Pavlova
Anastasia V. Pavlova
Ivan V. Zvyagin
Ivan V. Zvyagin
Ivan V. Zvyagin
Mikhail Shugay
Mikhail Shugay
Detecting T-cell clonal expansions and quantifying clone survival using deep profiling of immune repertoires
Frontiers in Immunology
T cell repertoire analysis
adaptive immune receptor repertoire (AIRR)
T cell receptor (TCR)
clonal tracking
hematopoietic (stem) cell transplantation (HCST)
immune reconstitution
title Detecting T-cell clonal expansions and quantifying clone survival using deep profiling of immune repertoires
title_full Detecting T-cell clonal expansions and quantifying clone survival using deep profiling of immune repertoires
title_fullStr Detecting T-cell clonal expansions and quantifying clone survival using deep profiling of immune repertoires
title_full_unstemmed Detecting T-cell clonal expansions and quantifying clone survival using deep profiling of immune repertoires
title_short Detecting T-cell clonal expansions and quantifying clone survival using deep profiling of immune repertoires
title_sort detecting t cell clonal expansions and quantifying clone survival using deep profiling of immune repertoires
topic T cell repertoire analysis
adaptive immune receptor repertoire (AIRR)
T cell receptor (TCR)
clonal tracking
hematopoietic (stem) cell transplantation (HCST)
immune reconstitution
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1321603/full
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