1. Physics of Living Systems
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Early life imprints the hierarchy of T cell clone sizes

  1. Mario U Gaimann
  2. Maximilian Nguyen
  3. Jonathan Desponds
  4. Andreas Mayer  Is a corresponding author
  1. Ludwig Maximilian University of Munich, Germany
  2. Princeton University, United States
  3. NSF-Simons Center for Quantitative Biology, Northwestern University, United States
Research Article
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Cite this article as: eLife 2020;9:e61639 doi: 10.7554/eLife.61639

Abstract

The adaptive immune system responds to pathogens by selecting clones of cells with specific receptors. While clonal selection in response to particular antigens has been studied in detail, it is unknown how a lifetime of exposures to many antigens collectively shape the immune repertoire. Here, using mathematical modeling and statistical analyses of T cell receptor sequencing data we develop a quantitative theory of human T cell dynamics compatible with the statistical laws of repertoire organization. We find that clonal expansions during a perinatal time window leave a long-lasting imprint on the human T cell repertoire, which is only slowly reshaped by fluctuating clonal selection during adult life. Our work provides a mechanism for how early clonal dynamics imprint the hierarchy of T cell clone sizes with implications for pathogen defense and autoimmunity.

Article and author information

Author details

  1. Mario U Gaimann

    Arnold Sommerfeld Center for Theoretical Physics and Center for NanoScience, Department of Physics, Ludwig Maximilian University of Munich, München, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2789-090X
  2. Maximilian Nguyen

    Lewis-Sigler Institute, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Jonathan Desponds

    NSF-Simons Center for Quantitative Biology, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7112-3217
  4. Andreas Mayer

    Lewis-Sigler Institute, Princeton University, Princeton, United States
    For correspondence
    andimscience@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6643-7622

Funding

Lewis-Sigler Institute (Lewis-Sigler fellowship)

  • Andreas Mayer

Deutscher Akademischer Austauschdienst (RISE fellowship)

  • Mario U Gaimann

Simons Foundation (SFARI/597491-RWC)

  • Jonathan Desponds

National Science Foundation (17764421)

  • Jonathan Desponds

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

Reviewing Editor

  1. Armita Nourmohammad, University of Washington, United States

Publication history

  1. Received: July 31, 2020
  2. Accepted: December 20, 2020
  3. Accepted Manuscript published: December 21, 2020 (version 1)
  4. Accepted Manuscript updated: January 5, 2021 (version 2)

Copyright

© 2020, Gaimann 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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