Early life imprints the hierarchy of T cell clone sizes
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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Further reading
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- Cell Biology
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- Cell Biology
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Cell-generated forces play a major role in coordinating the large-scale behavior of cell assemblies, in particular during development, wound healing, and cancer. Mechanical signals propagate faster than biochemical signals, but can have similar effects, especially in epithelial tissues with strong cell–cell adhesion. However, a quantitative description of the transmission chain from force generation in a sender cell, force propagation across cell–cell boundaries, and the concomitant response of receiver cells is missing. For a quantitative analysis of this important situation, here we propose a minimal model system of two epithelial cells on an H-pattern (‘cell doublet’). After optogenetically activating RhoA, a major regulator of cell contractility, in the sender cell, we measure the mechanical response of the receiver cell by traction force and monolayer stress microscopies. In general, we find that the receiver cells show an active response so that the cell doublet forms a coherent unit. However, force propagation and response of the receiver cell also strongly depend on the mechano-structural polarization in the cell assembly, which is controlled by cell–matrix adhesion to the adhesive micropattern. We find that the response of the receiver cell is stronger when the mechano-structural polarization axis is oriented perpendicular to the direction of force propagation, reminiscent of the Poisson effect in passive materials. We finally show that the same effects are at work in small tissues. Our work demonstrates that cellular organization and active mechanical response of a tissue are key to maintain signal strength and lead to the emergence of elasticity, which means that signals are not dissipated like in a viscous system, but can propagate over large distances.