Elucidation of T cell signalling models |
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| Authors: | Nick D.L. Owens Jon Timmis Andrew Greensted |
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| Affiliation: | a Department of Electronics, University of York, UK
b Department of Computer Science, University of York, UK |
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| Abstract: | A potential mechanism that allows T cells to reliably discriminate pMHC ligands involves an interplay between kinetic proofreading, negative feedback and a destruction of this negative feedback. We analyse a detailed model of these mechanisms which involves the TCR, SHP1 and ERK. We discover that the behaviour of pSHP1 negative feedback is of primary importance, and particularly the influence of a kinetic proofreading base negative feedback state on pSHP1 dynamics. The CD8 co-receptor is shown to benefit from a kinetic proofreading locking mechanism and is able to overcome pSHP1 negative influences to sensitise a T cell. |
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| Keywords: | T cell tunability Kinetic proofreading Negative feedback CD8, SHP1, ERK Stochastic modelling Continuous time Markov chain |
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