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Abstract
The relationship between biological research and mathematical modeling is complex, critical, and vital. In this review, we summarize the results of the collaboration between two laboratories, exploring the interaction between mathematical modeling and wet-lab immunology. During this collaboration several aspects of the immune defence against viral infections were investigated, focusing primarily on the subject of heterologous immunity. In this manuscript, we emphasize the topics where computational simulations were applied in conjunction with experiments, such as immune attrition, the growing and shrinking of cross-reactive T cell repertoires following repeated infections, the short and long-term effects of cross-reactive immunological memory, and the factors influencing the appearance of new clonal specificities. For each topic, we describe how the mathematical model used was adapted to answer specific biological questions, and we discuss the hypotheses that were generated by simulations. Finally, we propose rules for testing hypotheses that emerge from model experimentation in the wet lab, and vice-versa.
Acknowledgements
The copyright on the code of IMMSIM-C utilized throughout the research belongs to R. Puzone and his employer, IST (National Institute for Cancer Research). The expert secretarial assistance by Francesca Priarone and Elisa Tedone is gratefully acknowledged.
Declaration of interest: Research in this publication was supported by NIH/NIAID through Grant R01-AI054455 awarded to F. Celada. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.