T cell activation: Kinetic proofreading, serial engagement and cell adhesion

Coombs, Daniel; Goldstein, Byron

doi:10.1016/j.cam.2004.07.035

Cited by 26 publications

(23 citation statements)

References 75 publications

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“…At the time of activation of naive T-cell into cytotoxic or T-helper cells, the population of naive T-cells has to pass through the pattern recognition process of the identification of antigenic peptide sequences (self or non-self antigen), which in turn decides whether the naive T-cells will be converted into the active T-cells (which will further proliferate) or inactive Tcells (no further proliferation but the cells will survive) or dead T-cells (which will further trigger apoptotic pathway and cell death) (Carter 2000;Coombs and Goldstein 2005). Hence, certain deregulation of this sensitive mechanism can destabilize our body's immune system and can trigger various diseases, like auto-immune diseases, severe combined immune deficiency syndrome (SCID), etc.…”

Section: Introductionmentioning

confidence: 99%

Temporal protein expression pattern in intracellular signalling cascade during T-cell activation: A computational study

et al. 2015

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Various T-cell co-receptor molecules and calcium channel CRAC play a pivotal role in the maintenance of cell's functional responses by regulating the production of effector molecules (mostly cytokines) that aids in immune clearance and also maintaining the cell in a functionally active state. Any defect in these co-receptor signalling pathways may lead to an altered expression pattern of the effector molecules. To study the propagation of such defects with time and their effect on the intracellular protein expression patterns, a comprehensive and largest pathway map of T-cell activation network is reconstructed manually. The entire pathway reactions are then translated using logical equations and simulated using the published time series microarray expression data as inputs. After validating the model, the effect of in silico knock down of co-receptor molecules on the expression patterns of their downstream proteins is studied and simultaneously the changes in the phenotypic behaviours of the T-cell population are predicted, which shows significant variations among the proteins expression and the signalling routes through which the response is propagated in the cytoplasm. This integrative computational approach serves as a valuable technique to study the changes in protein expression patterns and helps to predict variations in the cellular behaviour.

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Section: Introductionmentioning

confidence: 99%

Temporal protein expression pattern in intracellular signalling cascade during T-cell activation: A computational study

et al. 2015

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“…On the other hand, if it remains bound too long it will activate those it encounters but the frequency of encounters will be small. The recognition that the pMHC-TCR bond half-life has opposing effects on kinetic proofreading and serial engagement led to the prediction that to achieve an optimal rate of TCR activation there should be an optimal half-life, or equivalently an optimal dissociation rate constant k off , (Coombs & Goldstein, 2005;Lanzavecchia et al, 1999). Although some studies have found an optimal half-life for T cell activation (Carreno et al, 2007;Coombs et al, 2002;Kalergis et al, 2001), there are other results that are not consistent with this model (reviewed in (Aleksic et al, 2010;Stone et al, 2009)).…”

Section: Introductionmentioning

confidence: 99%

Mathematical Modeling of Syk Activation in Allergen-Stimulated Mast Cells and Basophils

Nag¹,

Monine²,

Goldstein³

et al. 2012

Advances in Protein Kinases

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“…If the pMHC dissociates too rapidly, it will encounter many TCRs but activate few while if it remains bound too long it will activate those it encounters but encounters will be rare. The recognition that the pMHC-TCR bond half-life has opposite effects on kinetic proofreading and serial engagement led to the proposal that to achieve an optimal rate of TCR activation there should be an optimal half-life, or equivalently an optimal dissociation rate constant k off , [6, 7]. Although some studies have found an optimal half-life for T cell activation [8, 9, 10], there are other results that are inconsistent with this model (reviewed in [11, 12]).…”

Section: Introductionmentioning

confidence: 99%

A Detailed Mathematical Model Predicts That Serial Engagement of IgE–FcεRI Complexes Can Enhance Syk Activation in Mast Cells

Nag

Monine

Blinov

et al. 2010

The Journal of Immunology

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The term serial engagement was introduced to describe the ability of a single peptide, bound to a major histocompatibility complex molecule, to sequentially interact with T cell receptors within the contact region between a T cell and an antigen-presenting cell. In addition to ligands on surfaces, soluble multivalent ligands can serially engage cell surface receptors with sites on the ligand binding and dissociating from receptors many times before all ligand sites become free and the ligand leaves the surface. To evaluate the role of serial engagement in Syk activation we use a detailed mathematical model of the initial signaling cascade that is triggered when FcεRI is aggregated on mast cells by multivalent antigens. Although serial engagement is not required for mast cell signaling, it can influence the recruitment of Syk to the receptor and subsequent Syk phosphorylation. Simulating the response of mast cells to ligands that serially engage receptors at different rates shows that increasing the rate of serial engagement by increasing the rate of dissociation of the ligand-receptor bond decreases Syk phosphorylation. Increasing serial engagement by increasing the rate at which receptors are cross-linked, for example by increasing the forward rate constant for cross-linking or increasing the valence of the ligand, increases Syk phosphorylation. When serial engagement enhances Syk phosphorylation it does so by partially reversing the effects of kinetic proofreading. Serial engagement rapidly returns receptors that have dissociated from aggregates to new aggregates before the receptors have fully returned to their basal state.

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T cell activation: Kinetic proofreading, serial engagement and cell adhesion

Cited by 26 publications

References 75 publications

Temporal protein expression pattern in intracellular signalling cascade during T-cell activation: A computational study

Temporal protein expression pattern in intracellular signalling cascade during T-cell activation: A computational study

Mathematical Modeling of Syk Activation in Allergen-Stimulated Mast Cells and Basophils

A Detailed Mathematical Model Predicts That Serial Engagement of IgE–FcεRI Complexes Can Enhance Syk Activation in Mast Cells

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