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Updated: Jul 3, 2026
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T and B Cell Receptor Immune Repertoire Analysis using Next-generation Sequencing
Published on: January 12, 2021
Diversity, Equality, and Inclusion in the naïve T Cell Receptor Repertoire
Isabella Sodi1, Matthew V Cowley1, Trupti Gore1
1Institute of Infection, Immunity, and Transplantation, UCL, London, UK.
Immunological Reviews
|July 1, 2026
Summary
The human naïve T cell receptor (TCR) repertoire has millions of unique clonotypes, but their sizes are unequal. Mechanisms driving this T cell receptor diversity and tolerance require further investigation.
Area of Science:
- Immunology
- Computational Biology
- Genetics
Background:
- The T cell receptor (TCR) repertoire provides the foundation for adaptive immunity.
- Understanding the diversity and distribution of naïve TCR clonotypes is crucial for comprehending immune responses.
Purpose of the Study:
- To analyze the fundamental properties of the human naïve TCR repertoire, focusing on diversity, equality, and inclusion.
- To investigate the factors contributing to the unequal distribution of TCR clonotype sizes.
- To explore the role of tolerance mechanisms in shaping the naïve repertoire.
Main Methods:
- Combined experimental and computational approaches to estimate repertoire richness.
- Mathematical modeling and large-scale single-cell sequencing to analyze clonotype family sizes.
- Review of existing literature on thymic selection and alternative tolerance mechanisms.
Main Results:
- The human naïve TCR repertoire contains at least 100 million distinct clonotypes.
- Clonotype family sizes are highly unequal, with a few clonotypes dominating.
- Evidence for functional "holes" in the repertoire due to negative selection is limited, suggesting alternative tolerance mechanisms are key.
Conclusions:
- The mechanisms driving the unequal frequency distribution of naïve TCR clone sizes remain poorly understood and warrant further research.
- Regulatory T cells and T cell quorum sensing may play significant roles in maintaining T cell tolerance.
- Further investigation is needed to understand the impact of TCR repertoire heterogeneity on primary immune responses and potential vulnerabilities.
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