T cell receptor repertoires of mice and humans are clustered in similarity networks around conserved public CDR3 sequences
Autor: | Peter D. Sun, Jinghua Lu, Irena Zaretsky, Irun R. Cohen, Alfred Singer, Erez Greenstein, François Van Laethem, Asaf Madi, Nir Friedman, Eric Shifrut, Asaf Poran, Shlomit Reich-Zeliger, Tomer Arnon |
---|---|
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Mouse QH301-705.5 Somatic cell Science Systems biology Receptors Antigen T-Cell alpha-beta Immunology Sequence Homology chemical and pharmacologic phenomena Biology medicine.disease_cause General Biochemistry Genetics and Molecular Biology Conserved sequence Autoimmunity 03 medical and health sciences Mice 0302 clinical medicine Immune system Genetic variation medicine Animals Cluster Analysis Humans Biology (General) Conserved Sequence Genetics lymphocyte subsets General Immunology and Microbiology General Neuroscience T-cell receptor Genetic Variation hemic and immune systems General Medicine Immune checkpoint 030104 developmental biology 030220 oncology & carcinogenesis Medicine CDR3 T cell receptor Research Article Computational and Systems Biology Human |
Zdroj: | eLife eLife, Vol 6 (2017) |
ISSN: | 2050-084X |
Popis: | 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. DOI: http://dx.doi.org/10.7554/eLife.22057.001 |
Databáze: | OpenAIRE |
Externí odkaz: |