Elucidation of T cell signalling models.
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.
Owens
Nick D L
ND
Department of Electronics, University of York, UK. ndlo100@ohm.york.ac.uk
Timmis
Jon
J
Greensted
Andrew
A
Tyrrell
Andy
A
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003198:Computer Simulation; D025461:Feedback, Physiological; D006801:Humans; D007700:Kinetics; D020935:MAP Kinase Signaling System / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology; D018448:Models, Immunological; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D013997:Time Factors
D011948:Receptors, Antigen, T-Cell