Informace o publikaci

Age-Related Decrease in TCR Repertoire Diversity Measured with Deep and Normalized Sequence Profiling

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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

Rok publikování 2014
Druh Článek v odborném periodiku
Časopis / Zdroj Journal of immunology
Fakulta / Pracoviště MU

Středoevropský technologický institut

Citace
Doi http://dx.doi.org/10.4049/jimmunol.1302064
Obor Endokrinologie, diabetologie, metabolismus, výživa
Klíčová slova T-CELL REPERTOIRE; RECEPTOR DIVERSITY; THYMIC INVOLUTION; IMMUNE DEFENSE; OLD PRIMATES; IFN-GAMMA; TNF-ALPHA; RESPONSES; HOMEOSTASIS; GENERATION
Popis 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.
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