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How a well-adapted immune system is organized.

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.

SUBMITTER: Mayer A

PROVIDER: S-EPMC4434741 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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How a well-adapted immune system is organized.

Mayer Andreas A Balasubramanian Vijay V Mora Thierry T Walczak Aleksandra M AM

Proceedings of the National Academy of Sciences of the United States of America 20150427 19

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 en ...[more]

PMID: 25918407

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How a well-adapted immune system is organized.

Publications

How a well-adapted immune system is organized.

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