期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 112, 期 19, 页码 5950-5955出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1421827112
关键词
immune repertoires; optimal coding; repertoire diversity; competitive exclusion; jamming
资金
- European Research Council [306312]
- Fondation Pierre-Gilles de Gennes
- National Science Foundation (NSF) [PHY-1058202, EF-0928048]
- NSF [PHY-1066293]
- German Academic Exchange Service (DAAD)
- Direct For Mathematical & Physical Scien
- Division Of Physics [1058202] Funding Source: National Science Foundation
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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