ArticleProceedings of the National Academy of Sciences of the United States of America2012
Chromatin conformation governs T-cell receptor Jβ gene segment usage.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed.
- The Thymic Microenvironment Shapes Age-Related Qualitative Changes in the TCR Repertoire.Aging cell · 2026Article
- HTGTS-TCR-Seq for Profiling of Mouse and Human T-Cell Receptor α and β Gene Rearrangements and Diversity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Multi-omics profiling and experimental verification of tertiary lymphoid structure-related genes: molecular subgroups, immune infiltration, and prognostic implications in lung adenocarcinoma.Frontiers in immunology · 2024Article
- Peripheral T cell activation, not thymic selection, expands the T follicular helper repertoire in a lupus-prone murine model.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Profiling the epigenetic landscape of the antigen receptor repertoire: the missing epi-immunogenomics data.Nature methods · 2023Article
- Mouse mammary tumor virus is implicated in severity of colitis and dysbiosis in the IL-10Microbiome · 2023Article
- Utility of Bulk T-Cell Receptor Repertoire Sequencing Analysis in Understanding Immune Responses to COVID-19.Diagnostics (Basel, Switzerland) · 2022Review
- A hierarchy of selection pressures determines the organization of the T cell receptor repertoire.Frontiers in immunology · 2022Article
- Deep generative selection models of T and B cell receptor repertoires with soNNia.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Selection influences naive CD8+ TCR-β repertoire sharing.Immunology · 2021Article
- Predicting recognition between T cell receptors and epitopes with TCRGP.PLoS computational biology · 2021Article
- CDR3α drives selection of the immunodominant Epstein Barr virus (EBV) BRLF1-specific CD8 T cell receptor repertoire in primary infection.PLoS pathogens · 2019Article
- T Cell Repertoire Evolution after Allogeneic Bone Marrow Transplantation: An Organizational Perspective.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2019Article
- Transcriptional programming and T cell receptor repertoires distinguish human lung and lymph node memory T cells.Communications biology · 2019Article
- Quantitative Prediction of the Landscape of T Cell Epitope Immunogenicity in Sequence Space.Frontiers in immunology · 2019Article
- The expanding role of systems immunology in decoding the T cell receptor repertoire.Current opinion in systems biology · 2018Article
- Profiling of the TCRβ repertoire in non-model species using high-throughput sequencing.Scientific reports · 2018Article
- High-throughput sequencing of the T-cell receptor repertoire: pitfalls and opportunities.Briefings in bioinformatics · 2018Article
- On statistical modeling of sequencing noise in high depth data to assess tumor evolution.Journal of statistical physics · 2018Article
- Predicting the spectrum of TCR repertoire sharing with a data-driven model of recombination.Immunological reviews · 2018Review
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T cells play fundamental roles in adaptive immunity, relying on a diverse repertoire of T-cell receptor (TCR) α and β chains. Diversity of the TCR β chain is generated in part by a random yet intrinsically biased combinatorial rearrangement of variable (Vβ), diversity (Dβ), and joining (Jβ) gene segments. The mechanisms that determine biases in gene segment use remain unclear. Here we show, using a high-throughput TCR sequencing approach, that a physical model of chromatin conformation at the DJβ genomic locus explains more than 80% of the biases in Jβ use that we measured in murine T cells. This model also predicts correctly how differences in intersegment genomic distances between humans and mice translate into differences in Jβ bias between TCR repertoires of these two species. As a consequence of these structural and other biases, TCR sequences are produced with different a priori frequencies, thus affecting their probability of becoming public TCRs that are shared among individuals. Surprisingly, we find that many more TCR sequences are shared among all five mice we studied than among only subgroups of three or four mice. We derive a necessary mathematical condition explaining this finding, which indicates that the TCR repertoire contains a core set of receptor sequences that are highly abundant among individuals, if their a priori probability of being produced by the recombination process is higher than a defined threshold. Our results provide evidence for an expanded role of chromatin conformation in VDJ rearrangement, from control of gene accessibility to precise determination of gene segment use.
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