Fallon, Lauffenburger, 2000

Model Status

This CellML model has been recoded to remove the reaction element. The model is known to run in PCEnv and COR and the results are close to those in the published paper which are generated by the original model. The units have been checked and are consistent. We suspect this model might generate the exact published results if the original initial conditions were used. As it is, the paper does not state all of these values, but instead it explains that these values are calculated throughout the simulation and subsequently fed back into the model.

Model Structure

Interleukin-2 (IL-2) is a growth factor which is secreted by activated T-cells and which is responsible for stimulating T-cell proliferation. Following the binding of the cell surface IL-2 receptor to its ligand, the entire receptor-ligand complex is internalised into sorting endosomes by endocytosis. Within these endosomes, the receptor-ligand complex may dissociate, and also, internal receptors and ligands may associate to form a new complex. Receptor associated ligand is then subject to lysosomal degradation, while free intracellular ligand is recycled back to extracellular ligand. In the absence of any ligand, cell surface receptors are maintained at a steady level by constitutive internalisation and biosynthesis rates. In the presence of ligand, there are positive feedback effects. Cell surface receptor-ligand complexes stimulate the synthesis of new receptors, and they also enhance cell proliferation.

Eric M. Fallon and Douglas A. Lauffenburger capture these IL-2 trafficking dynamics in their computational model (see the figure below). The model uses kinetic equations to describe receptor-ligand binding, internalisation and postendocytotic sorting of IL-2 and the IL-2-receptor complex. Model simulations are able to predict T-cell proliferation responses to IL-2.

The complete original paper reference is cited below:

Computational Model for Effects of Ligand/Receptor Binding Properties on Interleukin-2 Trafficking Dynamics and T Cell Proliferation Response, Eric M. Fallon and Douglas A. Lauffenburger, 2000, Biotechnology Progress , 16, 905-916. PubMed ID: 11027188

A schematic diagram of Fallon and Lauffenburger's 2000 computational model of IL-2-receptor binding and trafficking. The model follows the path of an extracellular ligand as it is bound to a cell surface receptor, internalised, degraded or recycled.