The T-cell receptor repertoire of wild mice

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 Shannons 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.