Fallon2000 - Interleukin-2 dynamics

ABSTRACT:

This a model from the article:
Computational model for effects of ligand/receptor binding properties oninterleukin-2 trafficking dynamics and T cell proliferation response.
Fallon EM, Lauffenburger DA. Biotechnol Prog 2000 Sep-Oct;16(5):905-16 11027188 ,
Abstract:
Multisubunit cytokine receptors such as the heterotrimeric receptor forinterleukin-2 (IL-2) are ubiquitous in hematopoeitic cell types of importance inbiotechnology and are crucial regulators of cell proliferation anddifferentiation behavior. Dynamics of cytokine/receptor endocytic traffickingcan significantly impact cell responses through effects of receptordown-regulation and ligand depletion, and in turn are governed byligand/receptor binding properties. We describe here a computational model fortrafficking dynamics of the IL-2 receptor (IL-2R) system, which is able topredict T cell proliferation responses to IL-2. This model comprises kineticequations describing binding, internalization, and postendocytic sorting of IL-2and IL-2R, including an experimentally derived dependence of cell proliferationrate on these properties. Computational results from this model predict thatIL-2 depletion can be reduced by decreasing its binding affinity for the IL-2Rbetagamma subunit relative to the alpha subunit at endosomal pH, as a result ofenhanced ligand sorting to recycling vis-a-vis degradation, and that an IL-2analogue with such altered binding properties should exhibit increased potencyfor stimulating the T cell proliferation response. These results are inagreement with our recent experimental findings for the IL-2 analogue termed 2D1[Fallon, E. M. et al. J. Biol. Chem. 2000, 275, 6790-6797]. Thus, this type ofmodel may enable prediction of beneficial cytokine/receptor binding propertiesto aid development of molecular design criteria for improvements in applicationssuch as in vivo cytokine therapies and in vitro hematopoietic cell bioreactors.

This model was taken from the CellML repository and automatically converted to SBML.
The original model was: Fallon EM, Lauffenburger DA. (2000) - version=1.0
The original CellML model was created by:
Catherine Lloyd
[e-mail]
The University of Auckland

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SUBMITTER: Lucian Smith 

PROVIDER: MODEL1006230001 | biostudies-other |

SECONDARY ACCESSION(S): 11027188

REPOSITORIES: biostudies-other