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Characterization and Monitoring of Antigen-Responsive T Cell Clones Using T Cell Receptor Gene Expression Analysis

Abstract : High-throughput T-cell receptor repertoire sequencing constitutes a powerful tool to study T cell responses at the clonal level. However, it does not give information on the functional phenotype of the responding clones and lacks a statistical framework for quantitative evaluation. To overcome this, we combined datasets from different experiments, all starting from the same blood samples. We used a novel, sensitive, UMI-based protocol to perform repertoire analysis on experimental replicates. Applying established bioinformatic routines for transcriptomic expression analysis we explored the dynamics of antigen-induced clonal expansion after in vitro stimulation, identified antigen-responsive clones, and confirmed their activation status using the expression of activation markers upon antigen re-challenge. We demonstrate that the addition of IL-4 after antigen stimulation drives the expansion of T cell clones encoding unique receptor sequences. We show that our approach represents a scalable, high-throughput immunological tool, which can be used to identify and characterize antigen-responsive T cells at clonal level.
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https://hal.inrae.fr/hal-03321413
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Submitted on : Tuesday, August 17, 2021 - 4:10:02 PM
Last modification on : Friday, August 20, 2021 - 3:26:57 AM

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Distributed under a Creative Commons Attribution 4.0 International License

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Sabrina Pollastro, Marie de Bourayne, Giulia Balzaretti, Aldo Jongejan, Barbera van Schaik, et al.. Characterization and Monitoring of Antigen-Responsive T Cell Clones Using T Cell Receptor Gene Expression Analysis. Frontiers in Immunology, Frontiers, 2021, 11, pp.1-11. ⟨10.3389/fimmu.2020.609624⟩. ⟨hal-03321413⟩

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