Fallon2000 - Interleukin-2 dynamics

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
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
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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.
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Computational model for effects of ligand/receptor binding properties on interleukin-2 trafficking dynamics and T cell proliferation response.
- Fallon EM, Lauffenburger DA
- Biotechnology progress , 0/ 2000 , Volume 16 , Issue 5 , pages: 905-916 , PubMed ID: 11027188
- Department of Chemical Engineering, Biotechnology Process Engineering Center, and Division of Bioengineering & Environmental Health, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
- 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-à-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.
Submitter of this revision: administrator
Modellers: administrator, Camille Laibe
Metadata information
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hasPart (1 statement)
hasProperty (1 statement)
isVersionOf (1 statement)
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- Model originally submitted by : Camille Laibe
- Submitted: Jun 23, 2010 10:11:49 AM
- Last Modified: Jan 30, 2018 10:50:31 AM
Revisions
-
Version: 3
- Submitted on: Jan 30, 2018 10:50:31 AM
- Submitted by: administrator
- With comment: Model name updated using online editor.
-
Version: 2
- Submitted on: Jun 25, 2010 1:00:33 PM
- Submitted by: Camille Laibe
- With comment: Current version of Fallon2000_IL2dynamics
-
Version: 1
- Submitted on: Jun 23, 2010 10:11:49 AM
- Submitted by: Camille Laibe
- With comment: Original import of Fallon2000_IL2dynamics
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: Variable used inside SBML models
Species | Initial Concentration/Amount |
---|---|
Cs 0 Cytokine receptor common subunit gamma ; Interleukin-2 ; Interleukin-2 receptor subunit beta ; interleukin-2 receptor complex ; plasma membrane |
1.0 mol |
Ri 0 Cytokine receptor common subunit gamma ; Interleukin-2 receptor subunit beta ; Interleukin-2 Receptor ; intracellular part |
300.0 mol |
Li 0 Interleukin-2 ; intracellular part |
0.01 mol |
Ld 0 Interleukin-2 |
1.0 mol |
Ci 0 Cytokine receptor common subunit gamma ; Interleukin-2 ; Interleukin-2 receptor subunit beta ; interleukin-2 receptor complex ; intracellular part |
1.0 mol |
Rs 0 Interleukin-2 receptor subunit beta ; Cytokine receptor common subunit gamma ; Interleukin-2 Receptor ; plasma membrane |
1500.0 mol |
Reactions | Rate | Parameters |
---|---|---|
Cs_0 => Ci_0 | COMpartment*ke*Cs_0 | ke = 0.04 1/(0.0166667*s) |
Ri_0 => Ci_0; Li_0 | COMpartment*kfe*Li_0*Ri_0 | kfe = 1.104E-4 0.06*nl/(mol*s) |
Li_0 => | COMpartment*kx*Li_0 | kx = 0.15 1/(0.0166667*s) |
Ci_0 => Ld_0 | COMpartment*kh*Ci_0 | kh = 0.035 1/(0.0166667*s) |
Ci_0 => Ri_0 | COMpartment*kre*Ci_0 | kre = 0.1104 1/(0.0166667*s) |
=> Rs_0; Cs_0 | COMpartment*ksyn*Cs_0 | ksyn = 0.0011 1/(0.0166667*s) |
Rs_0 => Ri_0 | COMpartment*kt*Rs_0 | kt = 0.007 1/(0.0166667*s) |
(added: 30 Jan 2018, 10:48:33, updated: 30 Jan 2018, 10:48:33)