Elucidation of T cell signalling models

作者：Owens Nick D L^*; Timmis Jon; Greensted Andrew; Tyrrell Andy

来源：Journal of Theoretical Biology, 2010, 262(3): 452-470.

DOI：10.1016/j.jtbi.2009.10.017

• T cell tunability
• Kinetic proofreading
• Negative feedback
• CD8, SHP1, ERK
• Stochastic modelling
• Continuous time Markov chain

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.

• 出版日期2010-2-7