How a well-adapted immune system is organized

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 minimize...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS Vol. 112; no. 19; p. 5950
Main Authors: Mayer, Andreas, Balasubramanian, Vijay, Mora, Thierry, Walczak, Aleksandra M
Format: Journal Article
Language:English
Published: United States 12.05.2015
Subjects:
Adaptive Immunity - physiology
Animals
Antigens - chemistry
B-Lymphocytes - immunology
Bacteria - immunology
Binding, Competitive
Humans
Immune System - physiology
Lymphocytes - cytology
Models, Biological
T-Lymphocytes - immunology
competitive exclusion
immune repertoires
repertoire diversity
jamming
optimal coding
ISSN:1091-6490, 1091-6490
Online Access:Get more information
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Summary: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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ISSN:1091-6490
1091-6490
DOI:10.1073/pnas.1421827112