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Mathematical modeling of T-cell activation kinetic

Abstract : T-cell activation is a crucial step in mounting of the immune response. The dynamics of T-cell receptor (TCR) specific recognition of peptide presented by major histocompatibility complex (MHC) molecule decides the fate of the T cell. Several biochemical interactions interfere resulting in a highly complex mechanism that would be difficult to understand without computer help. The aim of the present study was to define a mathematical model in order to approach the kinetics of monoclonal T-cell-specific activation. The reaction scheme was first described and the model was tested using experimental parameters from the published data. Simulations were concordant with experimental data showing proportional decrease of membrane TCR and production of interleukin-2 (IL-2). Agonist and antagonist peptides induce different levels of intracellular signal that could make the yes or no decision for entry to cell cycle. Different conditions (peptide concentrations, initial TCR density and exogenous IL-2 levels) can be tested. Several parameters are missing for parameters estimation and adjustment before it could be adapted for a polyclonal T-cell reaction model. However, the model should be of interest in setting experiments, simulation of clinical responses and optimization of preventive or therapeutic immunotherapy.
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Submitted on : Friday, January 22, 2010 - 2:25:20 PM
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Caroline Bidot, Frédéric Gruy, Claire-Sophie Haudin, Fatima Zahra El Hentati, Bernard Guy, et al.. Mathematical modeling of T-cell activation kinetic. Journal of Computational Biology, Mary Ann Liebert, 2008, 15 (1), pp.105-128. ⟨10.1089/cmb.2007.0125⟩. ⟨emse-00449722⟩



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