Early life imprints the hierarchy of T cell clone sizes
- Ludwig Maximilian University of Munich, Germany
- Princeton University, United States
- NSF-Simons Center for Quantitative Biology, Northwestern University, United States
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.
Data availability
No new data was generated in this study.
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Dynamics of individual T cell repertoires: from cord blood to centenariansZenodo repository, 826447.
Article and author information
Author details
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
- Armita Nourmohammad, University of Washington, United States
Version history
- Received: July 31, 2020
- Accepted: December 20, 2020
- Accepted Manuscript published: December 21, 2020 (version 1)
- Accepted Manuscript updated: January 5, 2021 (version 2)
- Version of Record published: February 8, 2021 (version 3)
- Version of Record updated: February 9, 2021 (version 4)
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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Early life imprints the hierarchy of T cell clone sizes
eLife 9:e61639.
https://doi.org/10.7554/eLife.61639
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