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Diversity and clonal selection in the human T-cell repertoire
- Qi, Qian, Liu, Yi, Cheng, Yong, Glanville, Jacob, Zhang, David, Lee, Ji-Yeun, Olshen, Richard A., Weyand, Cornelia M., Boyd, Scott D., Goronzy, Jörg J.
- Proceedings of the National Academy of Sciences of the United States of America 2014 v.111 no.36 pp. 13139-13144
- T-lymphocytes, elderly, high-throughput nucleotide sequencing, humans, immune response, statistical analysis, young adults
- Significance A decline in the diversity of the T-cell receptor repertoire owing to thymic involution has been implicated as causing defective immune responses in the elderly. By applying next-generation sequencing of replicate TCRB libraries from highly purified T-cell subsets, and using nonparametric statistical analysis, we obtain estimates of repertoire richness in the young adult that are higher than previously reported. Although contracting with age, the repertoire remains highly diverse. These data challenge the paradigm that thymic rejuvenation is needed to maintain diversity and prevent immune incompetence in the elderly. However, we observe an increasing inequality of clonal sizes with age even among naïve T cells. This clonal selection could result in biased and possibly autoreactive immune responses.