1. Computational and Systems Biology
  2. Immunology and Inflammation
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Primary and secondary anti-viral response captured by the dynamics and phenotype of individual T cell clones

  1. Anastasia A Minervina  Is a corresponding author
  2. Mikhail V Pogorelyy  Is a corresponding author
  3. Ekaterina A Komech
  4. Vadim K Karnaukhov
  5. Petra Bacher
  6. Elisa Rosati
  7. Andre Franke
  8. Dmitriy Chudakov
  9. Ilgar Z Mamedov
  10. Yuri B Lebedev
  11. Thierry Mora
  12. Aleksandra M Walczak
  1. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Federation
  2. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russia
  3. Skoltech, Russian Federation
  4. Kiel University, Germany
  5. École Normale Supérieure, France
Research Article
  • Cited 3
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Cite this article as: eLife 2020;9:e53704 doi: 10.7554/eLife.53704

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.

Article and author information

Author details

  1. Anastasia A Minervina

    Department of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation
    For correspondence
    aminervina@mail.ru
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9884-6351
  2. Mikhail V Pogorelyy

    Department of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation
    For correspondence
    m.pogorely@gmail.com
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0773-1204
  3. Ekaterina A Komech

    Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia
    Competing interests
    No competing interests declared.
  4. Vadim K Karnaukhov

    Center of Life Sciences, Skoltech, Moscow, Russian Federation
    Competing interests
    No competing interests declared.
  5. Petra Bacher

    Institute of Immunology, Kiel University, Kiel, Germany
    Competing interests
    No competing interests declared.
  6. Elisa Rosati

    Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2635-6422
  7. Andre Franke

    Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany
    Competing interests
    No competing interests declared.
  8. Dmitriy Chudakov

    Department of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0430-790X
  9. Ilgar Z Mamedov

    Department of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation
    Competing interests
    No competing interests declared.
  10. Yuri B Lebedev

    Department of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4554-4733
  11. Thierry Mora

    Laboratoire de Physique, École Normale Supérieure, Paris, France
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5456-9361
  12. Aleksandra M Walczak

    Laboratoire de Physique Theorique, École Normale Supérieure, Paris, France
    Competing interests
    Aleksandra M Walczak, Senior editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2686-5702

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).

Reviewing Editor

  1. Satyajit Rath, Indian Institute of Science Education and Research (IISER), India

Publication history

  1. Received: November 18, 2019
  2. Accepted: February 21, 2020
  3. Accepted Manuscript published: February 21, 2020 (version 1)
  4. Version of Record published: March 6, 2020 (version 2)

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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