Age-Related Decrease in TCR Repertoire Diversity Measured with Deep and Normalized Sequence Profiling
Abstract
The decrease of TCR diversity with aging has never been studied by direct methods. In this study, we combined high-throughput Illumina sequencing with unique cDNA molecular identifier technology to achieve deep and precisely normalized profiling of TCR β repertoires in 39 healthy donors aged 6–90 y. We demonstrate that TCR β diversity per 106 T cells decreases roughly linearly with age, with significant reduction already apparent by age 40. The percentage of naive T cells showed a strong correlation with measured TCR diversity and decreased linearly up to age 70. Remarkably, the oldest group (average age 82 y) was characterized by a higher percentage of naive CD4+ T cells, lower abundance of expanded clones, and increased TCR diversity compared with the previous age group (average age 62 y), suggesting the influence of age selection and association of these three related parameters with longevity. Interestingly, cross-analysis of individual TCR β repertoires revealed a set >10,000 of the most representative public TCR β clonotypes, whose abundance among the top 100,000 clones correlated with TCR diversity and decreased with aging.
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Reduced numbers of naïve T cells are associated with a less diverse TCR repertoire of the total T cell compartment.
“Reduced numbers of naïve T cells are associated with a less diverse TCR repertoire of the total T cell compartment [334]”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [334]
Naive CD4+ and CD8+ T cell receptor diversity diminishes with age.
“naive CD4+ and CD8+ TCR diversity diminishes as we age133.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [133]
PCR and sequencing errors can be identified using molecular barcoding during cDNA synthesis.
“PCR and sequencing errors can be identified using molecular barcoding during cDNA synthesis”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Britanova et al., 2014
Reduced numbers of naïve T cells are associated with a less diverse TCR repertoire of the total T lymphocyte compartment over time.
“Reduced number of naïve T cells are associated with a less diverse TCR repertoire of the total T lymphocyte compartment overtime [79].”
From Aging of the immune system: Focus on inflammation and vaccination (2016) · cites this paper as [79]
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- Authors
- Britanova, O. V., Putintseva, E. V., Shugay, M., Merzlyak, E. M., Turchaninova, M. A., Staroverov, D. B., Bolotin, D. A., Lukyanov, S., Bogdanova, E. A., Mamedov, I. Z., Lebedev, Y. B., & Chudakov, D. M.
- Affiliations
- Russian Academy of Sciences (RU)
- Shemiakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science , 117997 Moscow,
- Corresponding author
- Shugay, Mikhail
- Lukyanov, Sergey
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-03
- Volume
- 192
- Issue
- 6
- Pages
- 2689-2698
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2137890831
- Cited by
- 465
- References
- 60
- Citations by year
- 2026: 34 · 2025: 33 · 2024: 44 · 2023: 49 · 2022: 49 · 2021: 46 · 2020: 51 · 2019: 35 · 2018: 30 · 2017: 37 · 2016: 21 · 2015: 28 · 2014: 7
- FWCI
- 14.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Physical Sciences › Engineering › Biomedical Engineering › Artificial Immune Systems Applications
- Keywords
- T cell receptor beta repertoire, TCR diversity, aging, naive T cells, CD4+ T cells, T cell clonotypes, T cell clones, longevity, T cell receptor sequencing
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Amino Acid Sequence, Base Sequence, Child, Female, Flow Cytometry, Humans, Male, Middle Aged, T-Lymphocytes, Genetic Variation, CD4-Positive T-Lymphocytes, Receptors, Antigen, T-Cell, alpha-beta, Complementarity Determining Regions, Young Adult, High-Throughput Nucleotide Sequencing
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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