Cited by 215T-cell and B-cell ImmunologyArtificial Immune Systems Applicationsvaccines and immunoinformatics approaches

Estimating T-cell repertoire diversity: limitations of classical estimators and a new approach

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Laydon, Daniel J., Bangham, Charles R. M., Asquith, Becca·2015·Philosophical Transactions of the Royal Society B: Biological Sciences

Abstract

A highly diverse T-cell receptor (TCR) repertoire is a fundamental property of an effective immune system, and is associated with efficient control of viral infections and other pathogens. However, direct measurement of total TCR diversity is impossible. The diversity is high and the frequency distribution of individual TCRs is heavily skewed; the diversity therefore cannot be captured in a blood sample. Consequently, estimators of the total number of TCR clonotypes that are present in the individual, in addition to those observed, are essential. This is analogous to the ‘unseen species problem’ in ecology. We review the diversity (species richness) estimators that have been applied to T-cell repertoires and the methods used to validate these estimators. We show that existing approaches have significant shortcomings, and frequently underestimate true TCR diversity. We highlight our recently developed estimator, DivE, which can accurately estimate diversity across a range of immunological and biological systems.

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  • The distribution of TCR frequencies in an analyzed sample may not reflect the entire repertoire and likely changes with age, which hampers inferential estimates of overall richness.

    “The distribution of TCR frequencies in the analyzed sample does not necessarily reflect the distribution in the entire repertoire; moreover, the distribution is likely to change with age, hampering inferential estimates of overall richness”

    From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Laydon et al., 2015

  • No optimal solution currently exists for extrapolating TCR richness from small samples to the whole repertoire.

    “Currently, an optimal solution for the latter barrier does not exist”

    From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Laydon et al., 2015

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Research works printed but not linked: 1

  1. [35]Alberts B Johnson A Lewis J Raff M Roberts K Walter P 2002 Lymphocytes and the cellular basis of adaptive immunity. In Molecular biology of the cell (eds B Alberts et al.), 4th edn. New York, NY: Garland Science. Available at http://www.ncbi.nlm.nih.gov/books/NBK26921/.

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Authors
Laydon, D. J., Bangham, C. R. M., & Asquith, B.
Affiliations
Imperial College London (GB)
Corresponding author
Asquith, Becca
Venue
Philosophical Transactions of the Royal Society B: Biological Sciences
Published
2015-08-19
Volume
370
Issue
1675
Pages
20140291
ISSN
  • 0962-8436 (ISSN-L)
  • 1471-2970
OpenAlex
W2173617309
Cited by
215
References
94
Citations by year
2026: 12 · 2025: 13 · 2024: 18 · 2023: 23 · 2022: 22 · 2021: 19 · 2020: 24 · 2019: 29 · 2018: 23 · 2017: 15 · 2016: 13 · 2015: 4
FWCI
1.73
Type
journal article
Language
en
Open access
Locations
  • Philosophical Transactions of the Royal Society B Biological Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Wellcome Trust (100291, 103865/Z/14/Z, 103865)
  • Blood Cancer UK (12038)
  • Medical Research Council (MR/J007439/1, MR/K019090/1)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Physical Sciences › Engineering › Biomedical Engineering › Artificial Immune Systems Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
Keywords
T cell receptor repertoire, species richness estimators, TCR clonotypes, immune diversity, viral infection control
MeSH terms
Animals, Humans, Models, Genetic, Receptors, Antigen, T-Cell, T-Lymphocytes, Genetic Variation, Gene Rearrangement, T-Lymphocyte, Models, Immunological, Lymphocyte Count, Statistics, Nonparametric, Host-Pathogen Interactions

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