O. Dushek

Regulation of temporal cytokine production by co-stimulation receptors in TCR-T cells is lost in CAR-T cells

This study compares cytokine production kinetics in TCR-T cells and CAR-T cells with and without co-stimulation, finding that 2nd-generation CAR-T cells sustain cytokine production without co-stimulation.

Analysis of emergent bivalent antibody binding identifies the molecular reach as a critical determinant of SARS-CoV-2 neutralisation potency

This paper develops a bivalent binding model to analyze how molecular reach affects SARS-CoV-2 neutralization potency across antibodies.

Apoptosis-mediated ADAM10 activation removes a mucin barrier promoting T cell efferocytosis

The paper shows that ADAM10-mediated removal of mucins during T cell apoptosis enhances macrophage efferocytosis.

Using CombiCells, a platform enabling titration and combinatorial display of cell surface ligands, to study T cell antigen sensitivity by TCRs, CARs, and BiTEs

The paper uses CombiCells to compare T cell antigen sensitivity mediated by TCRs, CARs, and BiTEs and assess the impact of co-stimulation and co-inhibition receptors.

TCR/CD3-based synthetic antigen receptors (TCC) convey superior antigen sensitivity combined with high fidelity of activation

This study shows TCR/CD3-based synthetic antigen receptors (TCC) have superior antigen sensitivity and activation fidelity compared to second-generation CARs.

Tuning the potency and therapeutic window of ImmTAC molecules by affinity modulation

This paper investigates how altering affinity for target and CD3 affects the potency and specificity of ImmTAC molecules, finding that optimal activation occurs with strong TCR affinity and intermediate anti-CD3 affinity.

Solution structure and synaptic analyses reveal determinants of bispecific T cell engager potency

The paper evaluates TcE formats to determine how contact distance and flexibility affect their potency in forming immunological synapses.

Mechanical forces impair antigen discrimination by reducing differences in T cell receptor off-rates

The paper shows mechanical forces reduce T cell antigen discrimination by accelerating off-rates of higher-affinity antigens.

T-cell microvilli simulations show operation near packing limit and impact on antigen recognition.

The paper develops a model of T-cell microvilli dynamics to show they operate near packing limits and have a modest impact on antigen discrimination.

Inefficient exploitation of accessory receptors reduces the sensitivity of chimeric antigen receptors.

This study shows that CARs have lower antigen sensitivity than TCRs due to inefficient use of accessory receptors, and demonstrates ways to improve this sensitivity.

Differential impact of TNFRSF co-stimulation on CD8+ T cell cytokine production by feedback control of surface receptor expression

This study investigates how different TNFRSF co-stimulation receptors affect CD8+ T cell cytokine production, revealing that feedback control of surface receptor expression explains their differential impact.

Synthetic antigen presenting cells reveal the diversity and functional specialisation of extracellular vesicles composing the fourth signal of T cell immunological synapses.

This study uses synthetic antigen-presenting cells to analyze the composition and functional specialization of extracellular vesicles released during T cell immunological synapses.

Effects of common mutations in the SARS-CoV-2 Spike RBD domain and its ligand the human ACE2 receptor on binding affinity and kinetics

This study analyzes how common mutations in SARS-CoV-2 Spike RBD and human ACE2 affect binding affinity and kinetics, identifying their roles in transmission and immune escape.

Fluctuations in TCR and pMHC interactions regulate T cell activation

This study introduces a stochastic model of T cell activation showing that information from TCR-pMHC interactions, not binding strength, drives immune responses and suggests optimizing stochasticity could improve therapeutics.

Intrinsic disorder in the T cell receptor creates cooperativity and controls ZAP70 binding

This paper uses simulations to show how intrinsic disorder in T cell receptor chains leads to nonlinear signaling through entropy changes, affecting ZAP70 binding and cooperativity.

Allosteric activation of T-cell antigen receptor signalling by quaternary structure relaxation

This study identifies mutations that enhance TCR-CD3 signalling by loosening TCR{beta} and CD3{zeta} interactions, showing pMHC binding can induce allosteric changes and initiate signal propagation.

The discriminatory power of the T cell receptor

This study measures TCR discriminatory power against pMHC antigens and finds it is imperfect, with T cells responding to low-affinity self pMHC with KD ~1 mM.

T cells exhibit unexpectedly low discriminatory power and can respond to ultra-low affinity peptide-MHC ligands

The paper measures ultra-low TCR/pMHC affinities and finds T cells have low discriminatory power, requiring large affinity differences to trigger responses.

Determination of the molecular reach of the protein tyrosine phosphatase SHP-1

This study measures the molecular reach of PD-1 tethered SHP-1 complexes and shows how tethering affects substrate accessibility and enzyme activity.

Human CD8+ T cells exhibit a shared antigen threshold for different effector responses

The paper shows that different effector responses of human CD8+ T cells share a common antigen threshold across varying affinities and co-stimulatory conditions.

Regulated unbinding of ZAP70 at the T cell receptor by kinetic avidity

The paper shows that ZAP70 unbinding from TCR is regulated by kinetic avidity, allowing both signal fidelity and reversibility in T cell responses.

A tissue-like platform for studying engineered quiescent human T-cells’ interactions with dendritic cells

This paper develops a tissue-like platform to study interactions between engineered quiescent human T-cells and dendritic cells, demonstrating CD4 help and PD-1 checkpoint blockade effects.

Perfect adaptation of CD8+ T cell responses to constant antigen input over a wide range of affinity is overcome by costimulation

The paper shows that partial TCR downregulation in T cells leads to perfect adaptation to constant antigen stimulation, which can be overcome by costimulation.

Molecular flexibility of DNA as a key determinant of RAD51 recruitment

This study shows RAD51 binds faster to flexible single-stranded DNA than rigid DNA or double-stranded DNA, suggesting DNA flexibility aids in homologous recombination.

A cell-topography based mechanism for ligand discrimination by the T-cell receptor

This paper develops a model showing T-cell receptors discriminate ligands based on dwell-time in phosphatase-depleted contacts constrained by cell topography, predicting signaling potency without multi-step proof-reading.

The Influence of Molecular Reach and Diffusivity on the Efficacy of Membrane-Confined Reactions

The paper studies how molecular reach and diffusivity affect reaction efficacy in membrane-confined systems, showing that increasing reach can enhance or reduce efficacy depending on diffusion rates.