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. (C) 2009 Elsevier Ltd. All rights reserved.
Original language | English |
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Pages (from-to) | 452-470 |
Number of pages | 19 |
Journal | Journal of theoretical biology |
Volume | 262 |
Issue number | 3 |
DOIs | |
Publication status | Published - 7 Feb 2010 |
Keywords
- T cell tunability
- Kinetic proofreading
- Negative feedback
- CD8, SHP1, ERK
- Stochastic modelling
- Continuous time Markov chain
- LIGAND DISCRIMINATION
- STOCHASTIC SIMULATION
- RECEPTOR
- SPECIFICITY
- ANTIGEN
- ACTIVATION
- RESPONSES
- KINETICS
- MATRIX