T cell receptor repertoires of mice and humans are clustered in similarity networks around conserved public CDR3 sequences

Asaf Madi, Asaf Poran, Eric Shifrut, Shlomit Reich-Zeliger, Erez Greenstein, Irena Zaretsky, Tomer Arnon, Francois Van Laethem, Alfred Singer, Jinghua Lu, Peter D. Sun, Irun R. Cohen, Nir Friedman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

99 Scopus citations

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-TCRb 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.

Original languageEnglish
Article numbere22057
JournaleLife
Volume6
DOIs
StatePublished - 21 Jul 2017
Externally publishedYes

Funding

FundersFunder number
Federal German Ministry for Education and Research
MD Moross Institute for Cancer Research
National Cancer InstituteZIABC011111
Minerva Foundation
Israel Science Foundation
Planning and Budgeting Committee of the Council for Higher Education of Israel

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