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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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