Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
Tomer Arnon
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel; Department of Physics and Astronomy, Alfred University, Alfred, United States
Francois Van Laethem
Experimental Immunology Branch, National Cancer Institute, Bethesda, United States
Alfred Singer
Experimental Immunology Branch, National Cancer Institute, Bethesda, United States
Jinghua Lu
Structural Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Rockville, United States
Peter D Sun
Structural Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Rockville, United States
Irun R Cohen
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
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.
