# The T-cell receptor repertoire of wild mice

**Authors:** Jacob A Cohen, Simon Hunter-Barnett, Gayathri Nageswaran, Suzanne Byrne, Gemma Freeman, Matthew V Cowley, Benny Chain, Mark Viney

PMC · DOI: 10.1093/discim/kyag002 · Discovery Immunology · 2026-02-20

## TL;DR

This study explores how the T-cell receptor repertoires of wild mice vary with age, sex, and location, revealing insights into their immune system's adaptability.

## Contribution

The study provides a novel description of T-cell receptor repertoires in wild mice, linking immune diversity to environmental exposure.

## Key findings

- Wild mice maintain large TCR repertoires with consistent richness across age and sex.
- TCR diversity is influenced by a sex-by-age interaction, indicating more abundant clones in older mice.
- The findings suggest wild mice balance broad immune response capacity with strong responses to persistent pathogens.

## Abstract

Wild animals live in a pathogen-rich environment and are normally infected with a wide range of micro- and macro-parasites. Wild animals’ T cells are central to the effectiveness of their adaptive immune response in ameliorating the effect of these infections. Here, we have investigated the T-cell receptor (TCR) repertoire of wild mice to investigate how it varies in animals of different ages and sex and from different sites.

We sequenced the TCR alpha and beta chains of CD4+ and CD8+ T cells of 65 wild Mus musculus domesticus from two UK sites.

We analysed repertoire richness and diversity finding that wild mice have large TCR repertoires. Repertoire richness, which measures the breadth of the repertoire, was not significantly affected by mouse age or sex, suggesting that wild mice maintain the capacity to respond to novel antigens throughout their lives. In contrast, repertoire diversity (measured by Shannon’s index) was affected by a mouse sex-by-age interaction. This low diversity, coupled with constant richness, points to older mice having comparatively more highly abundant clones in their repertoires, perhaps due to chronic exposure to persistent pathogens in their environment.

These findings provide a novel description of the wild mouse TCR, revealing an immune system that balances maintaining a broad response capacity with developing strong, lasting responses to infections in the natural environment.

Graphical Abstract

## Linked entities

- **Species:** Mus musculus domesticus (taxon 10092)

## Full-text entities

- **Genes:** Trav6-3 (T cell receptor alpha variable 6-3) [NCBI Gene 328483] {aka Gm13948, Gm193, Gm4, TCR}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}
- **Diseases:** infections (MESH:D007239)
- **Species:** Mus musculus domesticus (western European house mouse, subspecies) [taxon 10092], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12994567/full.md

## References

47 references — full list in the complete paper: https://tomesphere.com/paper/PMC12994567/full.md

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Source: https://tomesphere.com/paper/PMC12994567