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T and B Cell Receptor Immune Repertoire Analysis using Next-generation Sequencing
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Quantifying selection in immune receptor repertoires.

Yuval Elhanati1, Anand Murugan2, Curtis G Callan3

  • 1Laboratoire de Physique Théorique, Unité Mixte de Recherche 8549 and.

Proceedings of the National Academy of Sciences of the United States of America
|June 20, 2014
PubMed
Summary
This summary is machine-generated.

T-cell receptor diversity arises from VDJ recombination and selection. Natural selection appears to anticipate immune challenges by influencing this process, shaping receptor repertoires before pathogen exposure.

Keywords:
T cellpublic repertoirestatistical inferencethymic selection

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Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Adaptive immunity relies on diverse T-cell receptors (TCRs) for pathogen recognition.
  • TCR diversity is generated through VDJ recombination and subsequent selection.
  • Understanding selection pressures on TCR repertoire is crucial for immunology.

Purpose of the Study:

  • To quantify the impact of selection on TCR sequence composition.
  • To investigate the interplay between VDJ recombination and selection.
  • To model the factors influencing TCR diversity and repertoire formation.

Main Methods:

  • Analysis of high-throughput sequencing data from human TCR β-chains.
  • Inference of selection factors using a probabilistic maximum likelihood method.
  • Quantification of selection effects on V/J gene choice, length, and amino acid composition.

Main Results:

  • Significant correlation found between VDJ recombination biases and inferred selection factors.
  • Diversity reduction observed during the selection process.
  • Inferred selection factors showed minimal variation across donors and T-cell types (naive/memory).

Conclusions:

  • Natural selection appears to pre-emptively influence the VDJ recombination process.
  • This suggests an anticipatory mechanism in shaping immune receptor repertoires.
  • The model accurately predicts shared TCR sequences, supporting a stochastic origin for public sequences.