Quantifying selection in immune receptor repertoires

Yuval Elhanati, Anand Murugan, Curtis Gove Callan, Thierry Mora, Aleksandra M. Walczak

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)9875-9880
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number27
DOIs
StatePublished - Jul 8 2014

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Public repertoire
  • Statistical inference
  • T cell
  • Thymic selection

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