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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434741/ https://www.ncbi.nlm.nih.gov/pubmed/25918407 http://dx.doi.org/10.1073/pnas.1421827112 |
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author | Mayer, Andreas Balasubramanian, Vijay Mora, Thierry Walczak, Aleksandra M. |
author_facet | Mayer, Andreas Balasubramanian, Vijay Mora, Thierry Walczak, Aleksandra M. |
author_sort | Mayer, Andreas |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4434741 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-44347412015-05-19 How a well-adapted immune system is organized Mayer, Andreas Balasubramanian, Vijay Mora, Thierry Walczak, Aleksandra M. Proc Natl Acad Sci U S A Physical Sciences 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. National Academy of Sciences 2015-05-12 2015-04-27 /pmc/articles/PMC4434741/ /pubmed/25918407 http://dx.doi.org/10.1073/pnas.1421827112 Text en Freely available online through the PNAS open access option. |
spellingShingle | Physical Sciences Mayer, Andreas Balasubramanian, Vijay Mora, Thierry Walczak, Aleksandra M. How a well-adapted immune system is organized |
title | How a well-adapted immune system is organized |
title_full | How a well-adapted immune system is organized |
title_fullStr | How a well-adapted immune system is organized |
title_full_unstemmed | How a well-adapted immune system is organized |
title_short | How a well-adapted immune system is organized |
title_sort | how a well-adapted immune system is organized |
topic | Physical Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434741/ https://www.ncbi.nlm.nih.gov/pubmed/25918407 http://dx.doi.org/10.1073/pnas.1421827112 |
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