ABSTRACT:
This a model from the article:
Computational model for effects of ligand/receptor binding properties on
interleukin-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 for
interleukin-2 (IL-2) are ubiquitous in hematopoeitic cell types of importance in
biotechnology and are crucial regulators of cell proliferation and
differentiation behavior. Dynamics of cytokine/receptor endocytic trafficking
can significantly impact cell responses through effects of receptor
down-regulation and ligand depletion, and in turn are governed by
ligand/receptor binding properties. We describe here a computational model for
trafficking dynamics of the IL-2 receptor (IL-2R) system, which is able to
predict T cell proliferation responses to IL-2. This model comprises kinetic
equations describing binding, internalization, and postendocytic sorting of IL-2
and IL-2R, including an experimentally derived dependence of cell proliferation
rate on these properties. Computational results from this model predict that
IL-2 depletion can be reduced by decreasing its binding affinity for the IL-2R
betagamma subunit relative to the alpha subunit at endosomal pH, as a result of
enhanced ligand sorting to recycling vis-a-vis degradation, and that an IL-2
analogue with such altered binding properties should exhibit increased potency
for stimulating the T cell proliferation response. These results are in
agreement 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 of
model may enable prediction of beneficial cytokine/receptor binding properties
to aid development of molecular design criteria for improvements in applications
such 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
c.lloyd@auckland.ac.nz
The University of Auckland
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To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
Camille Laibe 
