Quantifying selection in immune receptor repertoires

The efficient recognition of pathogens by the adaptive immune system relies on the diversity of receptors displayed at the surface of immune cells. T-cell receptor diversity results from an initial random DNA editing process, called VDJ recombination, followed by functional selection of cells accord...

Celý popis

Uložené v:
Podrobná bibliografia
Vydané v:Proceedings of the National Academy of Sciences - PNAS Ročník 111; číslo 27; s. 9875
Hlavní autori: Elhanati, Yuval, Murugan, Anand, Callan, Jr, Curtis G, Mora, Thierry, Walczak, Aleksandra M
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 08.07.2014
Predmet:
CD4-Positive T-Lymphocytes - immunology
Humans
Receptors, Antigen, T-Cell, alpha-beta - genetics
Selection, Genetic
public repertoire
thymic selection
statistical inference
T cell
ISSN:1091-6490, 1091-6490
On-line prístup:Zistit podrobnosti o prístupe
Tagy: Pridať tag
Žiadne tagy, Buďte prvý, kto otaguje tento záznam!
Popis
Shrnutí:The efficient recognition of pathogens by the adaptive immune system relies on the diversity of receptors displayed at the surface of immune cells. T-cell receptor diversity results from an initial random DNA editing process, called VDJ recombination, followed by functional selection of cells according to the interaction of their surface receptors with self and foreign antigenic peptides. Using high-throughput sequence data from the β-chain of human T-cell receptors, we infer factors that quantify the overall effect of selection on the elements of receptor sequence composition: the V and J gene choice and the length and amino acid composition of the variable region. We find a significant correlation between biases induced by VDJ recombination and our inferred selection factors together with a reduction of diversity during selection. Both effects suggest that natural selection acting on the recombination process has anticipated the selection pressures experienced during somatic evolution. The inferred selection factors differ little between donors or between naive and memory repertoires. The number of sequences shared between donors is well-predicted by our model, indicating a stochastic origin of such public sequences. Our approach is based on a probabilistic maximum likelihood method, which is necessary to disentangle the effects of selection from biases inherent in the recombination process.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1091-6490
1091-6490
DOI:10.1073/pnas.1409572111