Cited by 465T-cell and B-cell ImmunologySingle-cell and spatial transcriptomicsArtificial Immune Systems Applications

Age-Related Decrease in TCR Repertoire Diversity Measured with Deep and Normalized Sequence Profiling

Britanova, Olga V, Putintseva, Ekaterina V, Shugay, Mikhail, Merzlyak, Ekaterina M, Turchaninova, Maria A, Staroverov, Dmitriy B, Bolotin, Dmitriy A, Lukyanov, Sergey +4 more·2014·The Journal of Immunology

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.

Integrity signals

Registry

Crossref · 10.4049/jimmunol.1302064

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60 of 60 references verified0 citation errors · 0 not checkable

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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]”
  • 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].”

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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
Venue
The Journal of Immunology
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

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