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Updated: Apr 25, 2026
09:47
Generation of Human Alloantigen-specific T Cells from Peripheral Blood
Published on: November 21, 2014
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Diversity and clonal selection in the human T-cell repertoire
Qian Qi1, Yi Liu2, Yong Cheng3
1Divisions of Immunology and Rheumatology, Department of Medicine and.
Summary
Human T-cell receptor (TCR) diversity is vast, with millions of unique TCR beta (TCRB) sequences. While repertoire richness declines modestly with age, significant clonal expansions in naive T cells suggest altered immune regulation in the elderly.
Area of Science:
- Immunology
- Molecular Biology
- Gerontology
Background:
- T-cell receptor (TCR) diversity is crucial for recognizing diverse foreign antigens.
- TCR repertoire generation occurs in the thymus during early life and is maintained by homeostatic proliferation.
Purpose of the Study:
- To estimate the lower bound of unique TCR beta (TCRB) sequences in human repertoires.
- To investigate the impact of aging on TCR repertoire diversity and clonal composition.
Main Methods:
- Next-generation sequencing was employed to analyze TCRB sequences.
- Nonparametric statistical analysis and a modified Gini-Simpson index were used to assess repertoire richness and clonality.
Main Results:
- Minimal estimates revealed over 100 million unique TCRB sequences in young adults' naive T-cell repertoires.
- Repertoire richness showed a modest 2- to 5-fold decline in healthy elderly individuals.
- Aging significantly increased clonal size inequality, with large naive T-cell clones observed in the elderly.
Conclusions:
- A highly diverse TCR repertoire is maintained despite thymic involution.
- Peripheral selection processes lead to repertoire alterations with age, potentially impacting immune responses in the elderly.
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