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

^*Corresponding author for this work

Department of Computer Science

University of York

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

7 Citations (Scopus)

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.

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 - 07 Feb 2010

Keywords

CD8, SHP1, ERK
Continuous time Markov chain
Kinetic proofreading
Negative feedback
Stochastic modelling
T cell tunability
Humans
Major Histocompatibility Complex/immunology
MAP Kinase Signaling System/immunology
CD8-Positive T-Lymphocytes/immunology
T-Lymphocytes/enzymology
Feedback, Physiological
Models, Immunological
Animals
Time Factors
Computer Simulation
Receptors, Antigen, T-Cell/immunology
Signal Transduction/immunology
Kinetics

Access to Document

10.1016/j.jtbi.2009.10.017

Permanent link

Persistent link

Cite this

@article{afeccaf79a404910ad29051051f492a3,

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.",

keywords = "CD8, SHP1, ERK, Continuous time Markov chain, Kinetic proofreading, Negative feedback, Stochastic modelling, T cell tunability, Humans, Major Histocompatibility Complex/immunology, MAP Kinase Signaling System/immunology, CD8-Positive T-Lymphocytes/immunology, T-Lymphocytes/enzymology, Feedback, Physiological, Models, Immunological, Animals, Time Factors, Computer Simulation, Receptors, Antigen, T-Cell/immunology, Signal Transduction/immunology, Kinetics",

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

year = "2010",

month = feb,

day = "7",

doi = "10.1016/j.jtbi.2009.10.017",

language = "English",

volume = "262",

pages = "452--470",

journal = "Journal of Theoretical Biology",

issn = "0022-5193",

publisher = "Elsevier",

number = "3",

}

TY - JOUR

T1 - Elucidation of T cell signalling models

AU - Owens, Nick D.L.

AU - Timmis, Jon

AU - Greensted, Andrew

AU - Tyrrell, Andy

PY - 2010/2/7

Y1 - 2010/2/7

N2 - 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.

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.

KW - CD8, SHP1, ERK

KW - Continuous time Markov chain

KW - Kinetic proofreading

KW - Negative feedback

KW - Stochastic modelling

KW - T cell tunability

KW - Humans

KW - Major Histocompatibility Complex/immunology

KW - MAP Kinase Signaling System/immunology

KW - CD8-Positive T-Lymphocytes/immunology

KW - T-Lymphocytes/enzymology

KW - Feedback, Physiological

KW - Models, Immunological

KW - Animals

KW - Time Factors

KW - Computer Simulation

KW - Receptors, Antigen, T-Cell/immunology

KW - Signal Transduction/immunology

KW - Kinetics

UR - http://www.scopus.com/inward/record.url?scp=70450267460&partnerID=8YFLogxK

U2 - 10.1016/j.jtbi.2009.10.017

DO - 10.1016/j.jtbi.2009.10.017

M3 - Article

C2 - 19833137

AN - SCOPUS:70450267460

SN - 0022-5193

VL - 262

SP - 452

EP - 470

JO - Journal of Theoretical Biology

JF - Journal of Theoretical Biology

IS - 3

ER -

Elucidation of T cell signalling models

Abstract

Keywords

Access to Document

Permanent link

Other files and links

Fingerprint

Cite this