Functionally specialized human CD4+ T cell subsets express physicochemically distinct TCRs

  1. Sofia A Kasatskaya
  2. Kristin Ladell
  3. Evgeniy S Egorov
  4. Kelly L Miners
  5. Alexey N Davydov
  6. Maria Metsger
  7. Dmitry B Staroverov
  8. Elena K Matveishina
  9. Irina A Shagina
  10. Ilgar Z Mamedov
  11. Mark Izraelson
  12. Pavel V Shelyakin
  13. Olga V Britanova
  14. David A Price
  15. Dmitriy M Chudakov  Is a corresponding author
  1. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Federation
  2. Cardiff University School of Medicine, United Kingdom
  3. Central European Institute of Technology, Czech Republic
  4. Lomonosov Moscow State University, Russian Federation

Abstract

The organizational integrity of the adaptive immune system is determined by functionally discrete subsets of CD4+ T cells, but it has remained unclear to what extent lineage choice is influenced by clonotypically expressed T cell receptors (TCRs). To address this issue, we used a high-throughput approach to profile the ab TCR repertoires of human naive and effector/memory CD4+ T cell subsets, irrespective of antigen specificity. Highly conserved physicochemical and recombinatorial features were encoded on a subset-specific basis in the effector/memory compartment. Clonal tracking further identified forbidden and permitted transition pathways, mapping effector/memory subsets related by interconversion or ontogeny. Public sequences were largely confined to particular effector/memory subsets, including regulatory T cells (Tregs), which also displayed hardwired repertoire features in the naive compartment. Accordingly, these cumulative repertoire portraits establish a link between clonotype fate decisions in the complex world of CD4+ T cells and the intrinsic properties of somatically rearranged TCRs.

Data availability

All extracted repertoires and metadata are deposited in Figshare: https://figshare.com/s/2145b1b16c6854445af7 and https://figshare.com/s/84ec5f412356afb0536d.

The following data sets were generated

Article and author information

Author details

  1. Sofia A Kasatskaya

    Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  2. Kristin Ladell

    Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Evgeniy S Egorov

    Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  4. Kelly L Miners

    Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Alexey N Davydov

    Adaptive Immunity Group, Central European Institute of Technology, Brno, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  6. Maria Metsger

    Adaptive Immunity Group, Central European Institute of Technology, Brno, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  7. Dmitry B Staroverov

    Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  8. Elena K Matveishina

    Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4641-4906
  9. Irina A Shagina

    Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  10. Ilgar Z Mamedov

    Department of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  11. Mark Izraelson

    Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  12. Pavel V Shelyakin

    Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  13. Olga V Britanova

    Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  14. David A Price

    Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9416-2737
  15. Dmitriy M Chudakov

    Department of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation
    For correspondence
    chudakovdm@mail.ru
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0430-790X

Funding

Ministry of Science and Higher Eductaion of Russian Federation (075-15-2019-1789)

  • Dmitriy M Chudakov

Wellcome Trust (100326/Z/12/Z)

  • David A Price

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: Ethical approval was granted by the institutional review committees at Cardiff University School of Medicine (reference number 16/55) and the Pirogov Russian National Research Medical University (protocol number 2017/52) and all donors provided informed consent for their participation in the study.

Reviewing Editor

  1. Armita Nourmohammad, University of Washington, United States

Publication history

  1. Received: March 19, 2020
  2. Accepted: December 4, 2020
  3. Accepted Manuscript published: December 8, 2020 (version 1)
  4. Version of Record published: December 30, 2020 (version 2)

Copyright

© 2020, Kasatskaya 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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  1. Sofia A Kasatskaya
  2. Kristin Ladell
  3. Evgeniy S Egorov
  4. Kelly L Miners
  5. Alexey N Davydov
  6. Maria Metsger
  7. Dmitry B Staroverov
  8. Elena K Matveishina
  9. Irina A Shagina
  10. Ilgar Z Mamedov
  11. Mark Izraelson
  12. Pavel V Shelyakin
  13. Olga V Britanova
  14. David A Price
  15. Dmitriy M Chudakov
(2020)
Functionally specialized human CD4+ T cell subsets express physicochemically distinct TCRs
eLife 9:e57063.
https://doi.org/10.7554/eLife.57063

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