Journal Article

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

Balzaretti, Giulia, Netherlands Organization for Health Research and Development 436001001, Maillère, Bernard, de Bourayne, Marie, Niewold, Ilse, T G, Médicaments et Technologies pour la Santé (MTS) ; Université Paris-Saclay-Institut des Sciences du Vivant Frédéric JOLIOT (JOLIOT) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Pollastro, Sabrina, Jongejan, Aldo, van Kampen, Antoine, H C, European Project: 115303,EC:FP7:SP1-JTI,IMI-JU-03-2010,ABIRISK, de Vries, Niek, Amsterdam University Medical Centers (Amsterdam UMC), van Schaik, Barbera, D C

2021

Overview

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.

• Publisher: HAL CCSD,Frontiers,Frontiers Media SA,Frontiers Media S.A
• Subject: adaptive immune receptor repertoire / Antigens / bioinformatics / Cloning / Cytokines / Gene expression / Genotype & phenotype / immunoinformatics / Immunology / Life Sciences / Lymphocytes / Lymphocytes T / next generation sequencing / Peptides / Phenotypes / T cell receptors / T cell responses / T-cell receptor / Transcriptomics
• ISBN: 0006258006000