Abstract

Mathematical models devised to simulate competition of species for a survival resource can also be used to model the competition of T cell clonotypes for stimulus from self-pMHC complexes. A clonotype is analogous to a species that receives survival stimuli from different self-pMHC with different strengths. Thus, we can describe the T cell repertoire as a set of naive clones that are crossreactive. By studying this model we obtain informative statistics such as the mean time to extinction of a clonotype, which depends on the starting number of cells per clone and the number of self-pMHC that it can recognise. Next, we introduce viral peptides into the model, as survival resources that provide stimuli orders of magnitude stronger to that provided by self-pMHC, simulating the immune response to foreign antigens. With this addition to the model we study the effect of such perturbations on the distribution of clonal sizes. The model will be updated to include naive, effector and memory compartments of T cells, so that changes in the repertoire can be studied over the course of more than one infection. An application of this model is in the study of Influenza A viruses, where research is being done on immune response to a second exposure to a different strain.

Recommended citation: Daniel F Luque Duque, Carmen Molina-Paris, Grant Lythe, Martin Lopez Garcia, Paul Glyndwr Thomas, Jessica Gaevert, Stochastic modelling of the T cell repertoire with epitope affinity, The Journal of Immunology, Volume 204, Issue 1_Supplement, May 2020, Page 94.18,
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