Elucidation of T cell signalling models

Nick D.L. Owens*, Jon Timmis, Andrew Greensted, Andy Tyrrell

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (SciVal)

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 languageEnglish
Pages (from-to)452-470
Number of pages19
JournalJournal of Theoretical Biology
Volume262
Issue number3
DOIs
Publication statusPublished - 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

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