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Insights into immune system development and function from mouse T-cell repertoires.

Zachary Sethna1, Yuval Elhanati1,2, Crissy S Dudgeon3

  • 1Joseph Henry Laboratories, Princeton University, Princeton, NJ 08544.

Proceedings of the National Academy of Sciences of the United States of America
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Summary

The adaptive immune system

Keywords:
T cellsVDJ recombinationimmunologymousesequencing

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Area of Science:

  • Immunology
  • Molecular Biology
  • Developmental Biology

Background:

  • Adaptive immunity relies on diverse immune cell surface receptors.
  • Receptor diversity arises from stochastic VDJ recombination during immune cell development.

Purpose of the Study:

  • To quantify age-related changes in VDJ recombination.
  • To understand the statistical impact of selection on T-cell receptor repertoires.

Main Methods:

  • Analysis of T-cell receptor (TCR) sequence repertoires from mouse blood and thymus.
  • Statistical deconvolution of mixed repertoires to infer temporal immune system evolution.

Main Results:

  • VDJ recombination shows increased insertions and diversity with age.
  • Selection primarily impacts TCR protein folding, not repertoire diversity.
  • Selection is less pronounced in mice than in humans.

Conclusions:

  • VDJ recombination dynamics evolve significantly from embryonic to adult stages.
  • Selection acts on TCR protein structure, ensuring functional receptor generation.
  • Comparative analysis reveals species-specific differences in immune repertoire selection.