Early life imprints the hierarchy of T cell clone sizes

Abstract
Data availability
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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.

The following previously published data sets were used

1. Britanova et al
(2016) Dynamics of individual T cell repertoires: from cord blood to centenarians
Zenodo repository, 826447.

https://doi.org/10.5281/zenodo.826447
1. Emerson et al
(2017) Immunosequencing identifies signatures of cytomegalovirus exposure history and HLA-mediated effects on the T cell repertoire
immunoACCESS repository.

https://doi.org/10.21417/B7001Z
1. Chu et al
(2019) Longitudinal immunosequencing in healthy people reveals persistent T cell receptors rich in highly public receptors
immunoACCESS repository.

https://doi.org/10.21417/B7J01X
1. Lindau et al
(2019) Cytomegalovirus Exposure in the Elderly Does Not Reduce CD8 T Cell Repertoire Diversity
immunoACCESS repository.

https://doi.org/10.21417/PL2018JI

Article and author information

Author details

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.

"This ORCID iD identifies the author of this article:" 0000-0002-2789-090X
Maximilian Nguyen

Lewis-Sigler Institute, Princeton University, Princeton, United States

Competing interests
The authors declare that no competing interests exist.
Jonathan Desponds

NSF-Simons Center for Quantitative Biology, Northwestern University, Evanston, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-7112-3217
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.

"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.

Copyright

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.