Primary and secondary anti-viral response captured by the dynamics and phenotype of individual T cell clones
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Federation
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russia
- Skoltech, Russian Federation
- Kiel University, Germany
- École Normale Supérieure, France
Abstract
The diverse repertoire of T-cell receptors (TCR) plays a key role in the adaptive immune response to infections. Using TCR alpha and beta repertoire sequencing for T-cell subsets, as well as single-cell RNAseq and TCRseq, we track the concentrations and phenotypes of individual T-cell clones in response to primary and secondary yellow fever immunization — the model for acute infection in humans — showing their large diversity. We confirm the secondary response is an order of magnitude weaker, albeit ∼ 10 days faster than the primary one. Estimating the fraction of the T-cell response directed against the single immunodominant epitope, we identify the sequence features of TCRs that define the high precursor frequency of the two major TCR motifs specific for this particular epitope. We also show the consistency of clonal expansion dynamics between bulk alpha and beta repertoires, using a new methodology to reconstruct alpha-beta pairings from clonal trajectories.
Data availability
Sequencing data have been deposited in SRA under accession code PRJNA577794.
Article and author information
Author details
Anastasia A Minervina
Mikhail V Pogorelyy
Aleksandra M Walczak
Funding
European Research Council (Consolidator Grant no 724208)
- Thierry Mora
- Aleksandra M Walczak
Russian Science Foundation (15-15-00178)
- Anastasia A Minervina
- Mikhail V Pogorelyy
- Ekaterina A Komech
- Vadim K Karnaukhov
- Yuri B Lebedev
Russian Foundation for Basic Research (18-29-09132)
- Ilgar Z Mamedov
Russian Foundation for Basic Research (19-54-12011)
- Ilgar Z Mamedov
Deutsche Forschungsgemeinschaft (Exc2167)
- Petra Bacher
- Elisa Rosati
- Andre Franke
Deutsche Forschungsgemeinschaft (4096610003)
- Elisa Rosati
Ministry of Science and Higher Education of the Russian Federation (075-15-2019-1660)
- Dmitriy Chudakov
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: All donors gave written informed consent to participate in the study under the declaration of Helsinki. The blood was collected with informed consent in a certified diagnostics laboratory. The experimental protocol was approved by the Ethical Committee of the Pirogov Russian National Research Medical University, Russia (FLU0108, granted January 29, 2016).
Copyright
© 2020, Minervina et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Primary and secondary anti-viral response captured by the dynamics and phenotype of individual T cell clones
eLife 9:e53704.
https://doi.org/10.7554/eLife.53704
