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 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.
Laboratoire de Physique Théorique and.
Andreas
A
Mayer
Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, PA 19104; and Initiative for the Theoretical Sciences, The Graduate Center, The City University of New York, New York, NY 10016.
Vijay
V
Balasubramanian
Laboratoire de Physique Statistique, CNRS, Université Pierre et Marie Curie and École Normale Supérieure, 75005 Paris, France; thierry.mora@gmail.com.
Thierry
T
Mora
Laboratoire de Physique Théorique and.
Aleksandra M
AM
Walczak
D056704:Adaptive Immunity / Q000502:physiology*; D000818:Animals; D000941:Antigens / Q000737:chemistry; D001402:B-Lymphocytes / Q000276:immunology; D001419:Bacteria / Q000276:immunology; D001667:Binding, Competitive; D006801:Humans; D007107:Immune System / Q000502:physiology*; D008214:Lymphocytes / Q000166:cytology; D008954:Models, Biological; D013601:T-Lymphocytes / Q000276:immunology
D000941:Antigens
competitive exclusion; immune repertoires; jamming; optimal coding; repertoire diversity