ArticleNature communications2019
Molecular constraints on CDR3 for thymic selection of MHC-restricted TCRs from a random pre-selection repertoire.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 76 citations in OpenAlex.
- The Thymic Microenvironment Shapes Age-Related Qualitative Changes in the TCR Repertoire.Aging cell · 2026Article
- Thymic selection of the T cell receptor repertoire is biased toward autoimmunity in females.eLife · 2026Article
- T-cell receptor alpha to beta chains binding prediction.Briefings in bioinformatics · 2026Article
- Systemic T Cell Receptor Profiling Reveals Adaptive Immune Activation and Potential Immune Signatures of Diagnosis and Brain Atrophy in Epilepsy.Annals of clinical and translational neurology · 2026Article
- PD-1 deficiency reshapes the TCRβ repertoire and T-cell developmental programs associated with susceptibility to lupus-like autoimmunity.Frontiers in immunology · 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
- TCR repertoire shaping of naïve T cell subsets in human ontogeny.Frontiers in immunology · 2026Article
- HLA alleles shape distinct biases in the usage preferences of TCR VFrontiers in immunology · 2026Article
- Benchmarking unsupervised methods for inferring TCR specificity.NAR genomics and bioinformatics · 2025Review
- A pan-disease and population-level single-cell TCRαβ repertoire reference.Cell discovery · 2025Article
- T cell receptor cross-reactivity prediction improved by a comprehensive mutational scan database.Cell systems · 2025Article
- Defining the genetic determinants of CD8Science advances · 2025Article
- Comprehensive epitope mutational scan database enables accurate T cell receptor cross-reactivity prediction.bioRxiv : the preprint server for biology · 2025Article
- The Evolving T Cell Receptor Recognition Code: The Rules Are More Like Guidelines.Immunological reviews · 2025Review
- Comprehensive analysis of αβT-cell receptor repertoires reveals signatures of thymic selection.Frontiers in immunology · 2025Article
- Temporal TCR dynamics and epitope diversity mark recovery in severe COVID-19 patients.Frontiers in immunology · 2025Article
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- Viral infection reveals hidden sharing of TCR CDR3 sequences between individuals.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
The αβ T cell receptor (TCR) repertoire on mature T cells is selected in the thymus, but the basis for thymic selection of MHC-restricted TCRs from a randomly generated pre-selection repertoire is not known. Here we perform comparative repertoire sequence analyses of pre-selection and post-selection TCR from multiple MHC-sufficient and MHC-deficient mouse strains, and find that MHC-restricted and MHC-independent TCRs are primarily distinguished by features in their non-germline CDR3 regions, with many pre-selection CDR3 sequences not compatible with MHC-binding. Thymic selection of MHC-independent TCR is largely unconstrained, but the selection of MHC-specific TCR is restricted by both CDR3 length and specific amino acid usage. MHC-restriction disfavors TCR with CDR3 longer than 13 amino acids, limits positively charged and hydrophobic amino acids in CDR3β, and clonally deletes TCRs with cysteines in their CDR3 peptide-binding regions. Together, these MHC-imposed structural constraints form the basis to shape VDJ recombination sequences into MHC-restricted repertoires.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.