title: Age-related decrease in TCR repertoire diversity measured with deep and normalized sequence profiling.
abstract: 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 β repertoires in 39 healthy donors aged 6-90 y. We demonstrate that TCR β 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 β repertoires revealed a set >10,000 of the most representative public TCR β clonotypes, whose abundance among the top 100,000 clones correlated with TCR diversity and decreased with aging.
authors: Shemiakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science, 117997 Moscow, Russia;
authors: Olga V
authors: OV
authors: Britanova
authors: Ekaterina V
authors: EV
authors: Putintseva
authors: Mikhail
authors: M
authors: Shugay
authors: Ekaterina M
authors: EM
authors: Merzlyak
authors: Maria A
authors: MA
authors: Turchaninova
authors: Dmitriy B
authors: DB
authors: Staroverov
authors: Dmitriy A
authors: DA
authors: Bolotin
authors: Sergey
authors: S
authors: Lukyanov
authors: Ekaterina A
authors: EA
authors: Bogdanova
authors: Ilgar Z
authors: IZ
authors: Mamedov
authors: Yuriy B
authors: YB
authors: Lebedev
authors: Dmitriy M
authors: DM
authors: Chudakov
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000276:immunology*; D000595:Amino Acid Sequence; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002648:Child; D022801:Complementarity Determining Regions / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D014644:Genetic Variation / Q000276:immunology*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D022801:Complementarity Determining Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta