ArticleProceedings of the National Academy of Sciences of the United States of America2014
Diversity and clonal selection in the human T-cell repertoire.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 500 papers.
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Who cites it
500 citing papers in PubMed, 756 citations in OpenAlex.
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- Effect of Ocrelizumab on B- and T-Cell Receptor Repertoire Diversity in Patients With Relapsing Multiple Sclerosis From the Randomized Phase III OPERA Trial.Neurology(R) neuroimmunology & neuroinflammation · 2023Trial
- T cell immunomonitoring: a comparative analysis of traditional and novel methods to quantify and characterize human antigen-specific T cells.Nature protocols · 2026Review
- Functional heterogeneity and plasticity in naïve CD8 T cells drive superior effector and memory responses.The Journal of experimental medicine · 2026Article
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- Discovery of Post-Translationally Modified Epitopes in Autoimmunity: Someone Has to Fish so Everyone Can Eat.Immunological reviews · 2026Review
- HLA-II Expression Marks Activated and Clonally Expanded CD8International journal of molecular sciences · 2026Article
- The Thymic Microenvironment Shapes Age-Related Qualitative Changes in the TCR Repertoire.Aging cell · 2026Article
- Metabolic exhaustion and immune ageing in rheumatoid arthritis.Nature reviews. Rheumatology · 2026Review
- Structural T-Cell Receptor Analysis in the Age of Machine Learning.Immunological reviews · 2026Review
- Machine learning-based prediction of cross-immunity.Briefings in bioinformatics · 2026Article
- Antigen-experienced airway CD8Science advances · 2026Article
- Thymic selection of the T cell receptor repertoire is biased toward autoimmunity in females.eLife · 2026Article
- [Phenotypic and functional changes in endogenous T cells during the bystander effect in different disease states of lymphomas treated with CD19-targeted chimeric antigen receptor T cells].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2026Article
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- Integrated TCRγ Clonality Workflow for Molecular Diagnosis in HTLV-1 Carriers and Adult T-Cell Leukemia/Lymphoma.Diagnostics (Basel, Switzerland) · 2026Article
- The T Cell Receptor: Molecular Sensor, Therapeutic Mediator and Probabilistic Driver of Adaptive Immunity.Immunological reviews · 2026Review
- Diversity, Equality, and Inclusion in the naïve T Cell Receptor Repertoire.Immunological reviews · 2026Review
- Lung mucosal and systemic responses at single-cell resolution in an aerosolized Mycobacterium bovis BCG human challenge model.Cell reports. Medicine · 2026Article
440 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
T-cell receptor (TCR) diversity, a prerequisite for immune system recognition of the universe of foreign antigens, is generated in the first two decades of life in the thymus and then persists to an unknown extent through life via homeostatic proliferation of naïve T cells. We have used next-generation sequencing and nonparametric statistical analysis to estimate a lower bound for the total number of different TCR beta (TCRB) sequences in human repertoires. We arrived at surprisingly high minimal estimates of 100 million unique TCRB sequences in naïve CD4 and CD8 T-cell repertoires of young adults. Naïve repertoire richness modestly declined two- to fivefold in healthy elderly. Repertoire richness contraction with age was even less pronounced for memory CD4 and CD8 T cells. In contrast, age had a major impact on the inequality of clonal sizes, as estimated by a modified Gini-Simpson index clonality score. In particular, large naïve T-cell clones that were distinct from memory clones were found in the repertoires of elderly individuals, indicating uneven homeostatic proliferation without development of a memory cell phenotype. Our results suggest that a highly diverse repertoire is maintained despite thymic involution; however, peripheral fitness selection of T cells leads to repertoire perturbations that can influence the immune response in the elderly.
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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.