How a well-adapted immune system is organized

Andreas Mayer; Vijay Balasubramanian; Thierry Mora; Aleksandra M. Walczak

doi:10.1073/pnas.1421827112

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arXiv · 1407.6888

How a well-adapted immune system is organized

Andreas Mayer·Vijay Balasubramanian·Thierry Mora·Aleksandra M. Walczak

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Abstract

The repertoire of lymphocyte receptors in the adaptive immune system protects organisms from diverse pathogens. A well-adapted repertoire should be tuned to the pathogenic environment to reduce the cost of infections. We develop a general framework for predicting the optimal repertoire that minimizes the cost of infections contracted from a given distribution of pathogens. The theory predicts that the immune system will have more receptors for rare antigens than expected from the frequency of encounters; individuals exposed to the same infections will have sparse repertoires that are largely different, but nevertheless exploit cross-reactivity to provide the same coverage of antigens; and the optimal repertoires can be reached via the dynamics of competitive binding of antigens by receptors, and selective amplification of stimulated receptors. Our results follow from a tension between the statistics of pathogen detection, which favor a broader receptor distribution, and the effects of cross-reactivity, which tend to concentrate the optimal repertoire onto a few highly abundant clones. Our predictions can be tested in high throughput surveys of receptor and pathogen diversity.

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Andreas Mayer, Vijay Balasubramanian, Thierry Mora, Aleksandra M. Walczak. 2014-07-25. How a well-adapted immune system is organized. https://doi.org/10.1073/pnas.1421827112

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