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@article{1228049, author = {Britanova, O.V. and Putintseva, E.V. and Shugay, M. and Merzlyak, E.M. and Turchaninova, M.A. and Staroverov, D.B. and Bolotin, D.A. and Lukyanov, S. and Bogdanova, E.A. and Mamedov, I.Z. and Lebedev, Y.B. and Chudakov, Dmitriy}, article_location = {BETHESDA}, article_number = {6}, doi = {http://dx.doi.org/10.4049/jimmunol.1302064}, keywords = {T-CELL REPERTOIRE; RECEPTOR DIVERSITY; THYMIC INVOLUTION; IMMUNE DEFENSE; OLD PRIMATES; IFN-GAMMA; TNF-ALPHA; RESPONSES; HOMEOSTASIS; GENERATION}, language = {eng}, issn = {0022-1767}, journal = {Journal of immunology}, title = {Age-Related Decrease in TCR Repertoire Diversity Measured with Deep and Normalized Sequence Profiling}, volume = {192}, year = {2014} }
TY - JOUR ID - 1228049 AU - Britanova, O.V. - Putintseva, E.V. - Shugay, M. - Merzlyak, E.M. - Turchaninova, M.A. - Staroverov, D.B. - Bolotin, D.A. - Lukyanov, S. - Bogdanova, E.A. - Mamedov, I.Z. - Lebedev, Y.B. - Chudakov, Dmitriy PY - 2014 TI - Age-Related Decrease in TCR Repertoire Diversity Measured with Deep and Normalized Sequence Profiling JF - Journal of immunology VL - 192 IS - 6 SP - 2689-2698 EP - 2689-2698 PB - Williams & Wilkins SN - 00221767 KW - T-CELL REPERTOIRE KW - RECEPTOR DIVERSITY KW - THYMIC INVOLUTION KW - IMMUNE DEFENSE KW - OLD PRIMATES KW - IFN-GAMMA KW - TNF-ALPHA KW - RESPONSES KW - HOMEOSTASIS KW - GENERATION N2 - The decrease of TCR diversity with aging has never been studied by direct methods. In this study, we combined high-throughput Illumina sequencing with unique cDNA molecular identifier technology to achieve deep and precisely normalized profiling of TCR beta repertoires in 39 healthy donors aged 6-90 y. We demonstrate that TCR beta diversity per 10(6) T cells decreases roughly linearly with age, with significant reduction already apparent by age 40. The percentage of naive T cells showed a strong correlation with measured TCR diversity and decreased linearly up to age 70. Remarkably, the oldest group (average age 82 y) was characterized by a higher percentage of naive CD4(+) T cells, lower abundance of expanded clones, and increased TCR diversity compared with the previous age group (average age 62 y), suggesting the influence of age selection and association of these three related parameters with longevity. Interestingly, cross-analysis of individual TCR beta repertoires revealed a set >10,000 of the most representative public TCR beta clonotypes, whose abundance among the top 100,000 clones correlated with TCR diversity and decreased with aging. ER -
BRITANOVA, O.V., E.V. PUTINTSEVA, M. SHUGAY, E.M. MERZLYAK, M.A. TURCHANINOVA, D.B. STAROVEROV, D.A. BOLOTIN, S. LUKYANOV, E.A. BOGDANOVA, I.Z. MAMEDOV, Y.B. LEBEDEV and Dmitriy CHUDAKOV. Age-Related Decrease in TCR Repertoire Diversity Measured with Deep and Normalized Sequence Profiling. \textit{Journal of immunology}. BETHESDA: Williams \&{} Wilkins, 2014, vol.~192, No~6, p.~2689-2698. ISSN~0022-1767. Available from: https://dx.doi.org/10.4049/jimmunol.1302064.
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