Comprehensive assessment of T-cell receptor β-chain diversity in αβ T cells
Open accessAbstract
The adaptive immune system uses several strategies to generate a repertoire of T- and B-cell antigen receptors with sufficient diversity to recognize the universe of potential pathogens. In αβ T cells, which primarily recognize peptide antigens presented by major histocompatibility complex molecules, most of this receptor diversity is contained within the third complementarity-determining region (CDR3) of the T-cell receptor (TCR) α and β chains. Although it has been estimated that the adaptive immune system can generate up to 1016 distinct αβ pairs, direct assessment of TCR CDR3 diversity has not proved amenable to standard capillary electrophoresis-based DNA sequencing. We developed a novel experimental and computational approach to measure TCR CDR3 diversity based on single-molecule DNA sequencing, and used this approach to determine the CDR3 sequence in millions of rearranged TCRβ genes from T cells of 2 adults. We find that total TCRβ receptor diversity is at least 4-fold higher than previous estimates, and the diversity in the subset of CD45RO+ antigen-experienced αβ T cells is at least 10-fold higher than previous estimates. These methods should prove valuable for assessment of αβ T-cell repertoire diversity after hematopoietic cell transplantation, in states of congenital or acquired immunodeficiency, and during normal aging.
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- Authors
- Robins, H. S., Campregher, P. V., Srivastava, S. K., Wacher, A., Turtle, C. J., Kahsai, O., Riddell, S. R., Warren, E. H., & Carlson, C. S.
- Affiliations
- Fred Hutch Cancer Center (US)
- University of Washington (US)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2009-11-05
- Volume
- 114
- Issue
- 19
- Pages
- 4099-4107
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC2774550
- OpenAlex
- W2043071551
- Cited by
- 1,122
- References
- 31
- Citations by year
- 2026: 38 · 2025: 61 · 2024: 52 · 2023: 68 · 2022: 86 · 2021: 99 · 2020: 96 · 2019: 90 · 2018: 84 · 2017: 95 · 2016: 88 · 2015: 75 · 2014: 60 · 2013: 58 · 2012: 41
- FWCI
- 9.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Durham Research Online (Durham University) (acceptedVersion)
- Durham Research Online (Durham University) (submittedVersion)
- Durham Research Online (Durham University) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (CA015704, CA 18029, DK056465)
- National Cancer Institute (R01CA106512, CA18029, CA015704, CA106512, P30CA015704, P01CA018029)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK056465, DK056465)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- T cell receptor beta chain, CDR3 diversity, T cell receptor repertoire, alpha beta T cells, single-molecule DNA sequencing, TCR beta gene rearrangement, antigen-experienced T cells, CD45RO, hematopoietic stem cell transplantation, immunodeficiency, immunosenescence
- MeSH terms
- Adult, Base Sequence, DNA, Humans, Male, Molecular Sequence Data, Sequence Homology, Nucleic Acid, Genetic Variation, Gene Rearrangement, beta-Chain T-Cell Antigen Receptor, Polymerase Chain Reaction, T-Lymphocyte Subsets, Receptors, Antigen, T-Cell, alpha-beta, Leukocyte Common Antigens, Genes, T-Cell Receptor beta, Complementarity Determining Regions
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