T cell receptor repertoires of mice and humans are clustered in similarity networks around conserved public CDR3 sequences
- Weizmann Institute of Science, Israel
- Weizmann Institute, Israel
- National Cancer Institute, United States
- National Institute of Allergy and Infectious Diseases, United States
Abstract
Diversity of T cell receptor (TCR) repertoires, generated by somatic DNA rearrangements, is central to immune system function. However, the level of sequence similarity of TCR repertoires within and between species has not been characterized. Using network analysis of high-throughput TCR sequencing data, we found that abundant CDR3-TCRβ sequences were clustered within networks generated by sequence similarity. We discovered a substantial number of public CDR3-TCRβ segments that were identical in mice and humans. These conserved public sequences were central within TCR sequence-similarity networks. Annotated TCR sequences, previously associated with self-specificities such as autoimmunity and cancer, were linked to network clusters. Mechanistically, CDR3 networks were promoted by MHC-mediated selection, and were reduced following immunization, immune checkpoint blockade or aging. Our findings provide a new view of T cell repertoire organization and physiology, and suggest that the immune system distributes its TCR sequences unevenly, attending to specific foci of reactivity.
Data availability
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Young mice TCR repertoirePublicly available at NCBI Sequence Read Archive (accession no: SRP042610).
Article and author information
Author details
Funding
Minerva Foundation
- Nir Friedman
Federal German Ministry for Education and Research
- Nir Friedman
I-CORE
- Nir Friedman
Israel Science Foundation
- Nir Friedman
M.D. Moross Institute for Cancer Reseach
- Asaf Madi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Arup K Chakraborty, Ragon Institute of MGH, MIT and Harvard, United States
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#24110116-2) of the Weizmann Institute of Science. The protocol was approved by the Committee on the Ethics of Animal Experiments of the Weizmann Institute of Science. Every effort was made to minimize suffering.
Version history
- Received: October 10, 2016
- Accepted: July 14, 2017
- Accepted Manuscript published: July 21, 2017 (version 1)
- Version of Record published: August 11, 2017 (version 2)
Copyright
© 2017, Madi 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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T cell receptor repertoires of mice and humans are clustered in similarity networks around conserved public CDR3 sequences
eLife 6:e22057.
https://doi.org/10.7554/eLife.22057
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