Age-related decrease in TCR repertoire diversity measured with deep and normalized sequence profiling
Language: 
English
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 ? repertoires in 39 healthy donors aged 6-90 y. We demonstrate that TCR ? 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 ? repertoires revealed a set >10,000 of the most representative public TCR ? clonotypes, whose abundance among the top 100,000 clones correlated with TCR diversity and decreased with aging.

Author(s): 
Britanova, Olga V.
Putintseva, Ekaterina V.
Shugay, Mikhail
Merzlyak, Ekaterina M.
Turchaninova, Maria A.
Staroverov, Dmitriy B.
Bolotin, Dmitriy A.
Lukyanov, Sergey
Bogdanova, Ekaterina A.
Mamedov, Ilgar Z.
Lebedev, Yuriy B.
Chudakov, Dmitriy M.
Item Type: 
Journal Article
Publication Title: 
Journal of Immunology (Baltimore, Md.: 1950)
Journal Abbreviation: 
J. Immunol.
Publication Date: 
3/15/2014
Publication Year: 
2014
Pages: 
2689-2698
Volume: 
192
Issue: 
6
ISSN: 
1550-6606
DOI: 
10.4049/jimmunol.1302064
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 24510963

Turabian/Chicago Citation

Olga V. Britanova, Ekaterina V. Putintseva, Mikhail Shugay, Ekaterina M. Merzlyak, Maria A. Turchaninova, Dmitriy B. Staroverov, Dmitriy A. Bolotin, Sergey Lukyanov, Ekaterina A. Bogdanova, Ilgar Z. Mamedov, Yuriy B. Lebedev and Dmitriy M. Chudakov. 3/15/2014. "Age-related decrease in TCR repertoire diversity measured with deep and normalized sequence profiling." Journal of Immunology (Baltimore, Md.: 1950) 192: 6: 2689-2698. 10.4049/jimmunol.1302064.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.4049/jimmunol.1302064 | issn = 1550-6606 | volume = 192 | pages = 2689-2698 | last = Britanova | first = Olga V. | coauthors = Putintseva, Ekaterina V., Shugay, Mikhail, Merzlyak, Ekaterina M., Turchaninova, Maria A., Staroverov, Dmitriy B., Bolotin, Dmitriy A., Lukyanov, Sergey, Bogdanova, Ekaterina A., Mamedov, Ilgar Z., Lebedev, Yuriy B., Chudakov, Dmitriy M. | title = Age-related decrease in TCR repertoire diversity measured with deep and normalized sequence profiling | journal = Journal of Immunology (Baltimore, Md.: 1950) | date = 3/15/2014 | pmid = | pmc = }} </ref>