Elucidation of T cell signalling models

Research output: Contribution to journalArticlepeer-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 languageEnglish
Pages (from-to)452-470
Number of pages19
JournalJournal of theoretical biology
Volume262
Issue number3
DOIs
Publication statusPublished - 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

Cite this