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 -