Population variability in the generation and selection of T-cell repertoires

The diversity of T-cell receptor (TCR) repertoires is achieved by a combination of two intrinsically stochastic steps: random receptor generation by VDJ recombination, and selection based on the recognition of random self-peptides presented on the major histocompatibility complex. These processes le...

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Published in:PLoS computational biology Vol. 16; no. 12; p. e1008394
Main Authors: Sethna, Zachary, Isacchini, Giulio, Dupic, Thomas, Mora, Thierry, Walczak, Aleksandra M., Elhanati, Yuval
Format: Journal Article
Language:English
Published: United States Public Library of Science 01.12.2020
Public Library of Science (PLoS)
Subjects:
Adaptive Immunity
Biology and Life Sciences
Humans
Medicine and Health Sciences
Physical Sciences
Receptors, Antigen, T-Cell, alpha-beta - immunology
Receptors, Antigen, T-Cell, alpha-beta - metabolism
Research and Analysis Methods
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
V(D)J Recombination
ISSN:1553-7358, 1553-734X, 1553-7358
Online Access:Get full text
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Summary:The diversity of T-cell receptor (TCR) repertoires is achieved by a combination of two intrinsically stochastic steps: random receptor generation by VDJ recombination, and selection based on the recognition of random self-peptides presented on the major histocompatibility complex. These processes lead to a large receptor variability within and between individuals. However, the characterization of the variability is hampered by the limited size of the sampled repertoires. We introduce a new software tool SONIA to facilitate inference of individual-specific computational models for the generation and selection of the TCR beta chain (TRB) from sequenced repertoires of 651 individuals, separating and quantifying the variability of the two processes of generation and selection in the population. We find not only that most of the variability is driven by the VDJ generation process, but there is a large degree of consistency between individuals with the inter-individual variance of repertoires being about ∼2% of the intra-individual variance. Known viral-specific TCRs follow the same generation and selection statistics as all TCRs.
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The authors have declared that no competing interests exist.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1008394