Elucidation of T cell signalling models

Nick D. L. Owens; Jon Timmis; Andrew Greensted; Andy Tyrrell

doi:10.1016/j.jtbi.2009.10.017

Elucidation of T cell signalling models

Nick D. L. Owens, Jon Timmis, Andrew Greensted, Andy Tyrrell

Research output: Contribution to journal › Article › peer-review

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
Pages (from-to)	452-470
Number of pages	19
Journal	Journal of theoretical biology
Volume	262
Issue number	3
DOIs	https://doi.org/10.1016/j.jtbi.2009.10.017
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

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10.1016/j.jtbi.2009.10.017

http://www.sciencedirect.com/science/article/pii/S0022519309004925

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title = "Elucidation of T cell signalling models",

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.",

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author = "Owens, {Nick D. L.} and Jon Timmis and Andrew Greensted and Andy Tyrrell",

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AU - Timmis, Jon

AU - Greensted, Andrew

AU - Tyrrell, Andy

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AB - 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.

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KW - Negative feedback

KW - CD8, SHP1, ERK

KW - Stochastic modelling

KW - Continuous time Markov chain

KW - LIGAND DISCRIMINATION

KW - STOCHASTIC SIMULATION

KW - RECEPTOR

KW - SPECIFICITY

KW - ANTIGEN

KW - ACTIVATION

KW - RESPONSES

KW - KINETICS

KW - MATRIX

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VL - 262

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EP - 470

JO - Journal of Theoretical Biology

JF - Journal of Theoretical Biology

SN - 0022-5193

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ER -

Elucidation of T cell signalling models

Abstract

Keywords

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