The effects of interleukin-2 on immune response regulation.

The immune system has many adaptive and dynamic components that are regulated to ensure appropriate, precise and rapid response to a foreign pathogen. A delayed or inadequate immune response can lead to prolonged disease, while an excessive or under-regulated response can lead to autoimmunity. The cytokine, interleukin-2 (IL-2) and its receptor IL-2R play an important role in maintaining this balance.The IL-2 receptor transduces pSTAT5 signal through both the intermediate and high affinity receptors, which differ from each other by the presence of CD25 chain in IL-2 receptor. We present experimental data on the kinetics of pSTAT5 signalling through both of the receptors and develop a model that captures this kinetics. We then use this model to parameterize key aspects of two additional models in which we propose and study two different mechanisms by which IL-2 receptor can transduce distinct signals leading to either an activated or a non-activated cell state. We speculate that this initial state differentiation, perhaps enhanced by downstream feedbacks, may eventually lead to differential cell fates.Our result shows that non-linear dynamical models can suggest resolution of a puzzling array of seemingly contradictory experimental results on IL-2 effect on proliferation and differentiation of T-cells.

Induced Europium Circularly Polarized Luminescence Monitors Reversible Drug Binding to Native α1 -Acid Glycoprotein.

Alpha-1-acid glycoprotein (α1 -AGP) is an important blood plasma glycoprotein. Following an acute-phase reaction such as stress, inflammation, burn, or infection, the bloodstream concentration of α1 -AGP can increase up to 400 % of its normal concentration. A wide range of drugs is known to bind α1 -AGP. Increased binding of pharmacologically active compounds to α1 -AGP moderates their clinical effect by decreasing the amount of unbound drug in the bloodstream. This has important clinical ramifications for such applications as the duration of anesthesia and in determining dosage for drug therapy. In this study, the competitive binding to α1 -AGP of a dynamically racemic europium(III) complex with seven pharmacologically active drugs absorbing in the range λ 250-290 nm was monitored by following changes in europium total emission and in induced circularly polarized luminescence (CPL). Binding affinities corresponding to Kd values in the range 0.5-100 µm were measured, in good agreement with published data.

Encapsulation of an enzyme cascade within the bacteriophage P22 virus-like particle.

Developing methods for investigating coupled enzyme systems under conditions that mimic the cellular environment remains a significant challenge. Here we describe a biomimetic approach for constructing densely packed and confined multienzyme systems through the co-encapsulation of 2 and 3 enzymes within a virus-like particle (VLP) that perform a coupled cascade of reactions, creating a synthetic metabolon. Enzymes are efficiently encapsulated in vivo with known stoichiometries, and the kinetic parameters of the individual and coupled activities are characterized. From the results we develop and validate a mathematical model for predicting the expected kinetics for coupled reactions under co-localized conditions.