title: Computer simulations of heterologous immunity: highlights of an interdisciplinary cooperation.
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.
authors.affiliation: Division of Rheumatology, Department of Medicine, New York University School of Medicine, New York, NY, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Calcagno
authors.forename: Roberto
authors.initials: R
authors.lastname: Puzone
authors.forename: Yanthe E
authors.initials: YE
authors.lastname: Pearson
authors.forename: Yiming
authors.initials: Y
authors.lastname: Cheng
authors.forename: Dario
authors.initials: D
authors.lastname: Ghersi
authors.forename: Liisa K
authors.initials: LK
authors.lastname: Selin
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Welsh
authors.forename: Franco
authors.initials: F
authors.lastname: Celada
mesh_terms: D000818:Animals; D003198:Computer Simulation; D003429:Cross Reactions / Q000276:immunology; D006801:Humans; D007109:Immunity / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology; D058025:Interdisciplinary Studies