- Author:
- Catherine Lloyd <c.lloyd@auckland.ac.nz>
- Date:
- 2010-01-13 15:13:22+13:00
- Desc:
- Removed non-unicode compliant character from the abstract.
- Permanent Source URI:
- https://models.physiomeproject.org/workspace/fallon_lauffenburger_2000/rawfile/ea0210d2ea87dfa1fd021ab6ccb071a18fc0d480/fallon_lauffenburger_2000.cellml
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<title>Computational model for effects of ligand/receptor binding properties on interleukin-2 trafficking dynamics and T cell proliferation response</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Auckland Bioengineering Institute, The University of Auckland</shortaffil>
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<section id="sec_status">
<title>Model Status</title>
<para>
The model is known to run in PCEnv, OpenCell and COR and the results replicate the published paper (Figure 5), as generated by the original model. The units have been checked and are consistent.
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<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
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.
</para>
<para>
The original paper reference is cited below:
</para>
<para>
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, <emphasis>Biotechnology Progress</emphasis>, 16, 905-916. <ulink url="http://www.ncbi.nlm.nih.gov/pubmed/11027188">PubMed ID: 11027188</ulink>
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<caption>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.</caption>
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<map_variables variable_1="Ve" variable_2="Ve"/>
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<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"><rdf:Description rdf:about="rdf:#0ef470ea-1815-4857-949d-acaedee73d25"><Orgname xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">The University of Auckland</Orgname><Orgunit xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">The Bioengineering Institute</Orgunit></rdf:Description><rdf:Description rdf:about="rdf:#cc118e82-0b3d-4266-9cb0-eabbe16ea6e9"><rdf:type><rdf:Description rdf:about="http://www.w3.org/1999/02/22-rdf-syntax-ns#Seq"/></rdf:type><rdf:_1><rdf:Description rdf:about="rdf:#990c09ff-b3ac-4074-95cc-8044bcb735b5"/></rdf:_1><rdf:_2><rdf:Description rdf:about="rdf:#967cfc85-8837-45df-9bd3-82eebeea8c01"/></rdf:_2></rdf:Description><rdf:Description rdf:about="rdf:#5f0fdf18-d949-4855-89c8-5afe7e29c5d3"><JournalArticle xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:about="rdf:#1c28ecef-57c7-4dba-9912-dbda943ee013"/></JournalArticle><Pubmed_id xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">11027188</Pubmed_id></rdf:Description><rdf:Description rdf:about="rdf:#90819d10-f748-4d4a-b133-20b3723ea5f7"><Other xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">A</Other><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Autumn</Given><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Cuellar</Family></rdf:Description><rdf:Description rdf:about="rdf:#8da5fc98-677c-40bb-8d03-df54c3f9856b"><FN xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Catherine Lloyd</FN></rdf:Description><rdf:Description rdf:about="Ri"><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">intracellular IL-2 receptor</alternative><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Ri</title></rdf:Description><rdf:Description rdf:about="rdf:#16619619-4f05-442c-b41b-2f984451c437"><rdf:value xml:lang="en">This is the CellML description of Fallon and Lauffenburger's 2000
model of the effects of ligand-receptor binding properties on
interleukin-2 trafficking dynamics and T cell proliferation response.</rdf:value><creator xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:about="rdf:#b644be24-2643-4b75-8362-c68a12d52199"/></creator></rdf:Description><rdf:Description rdf:about="rdf:#6490193c-e115-4e50-a830-abfb9d3511c8"><Other xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">May</Other><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Catherine</Given><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Lloyd</Family></rdf:Description><rdf:Description rdf:nodeID="n1"><rdf:first><rdf:Description rdf:nodeID="n2"/></rdf:first><rdf:rest><rdf:Description rdf:about="http://www.w3.org/1999/02/22-rdf-syntax-ns#nil"/></rdf:rest></rdf:Description><rdf:Description rdf:about="rdf:#671acd9f-ea5e-46a9-a8d6-522b62c66e3b"><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#77d2f20d-ed49-4325-9474-ef7e6935396e"/></N></rdf:Description><rdf:Description rdf:about="rdf:#157e07e3-4e6d-4039-9a0e-39f8d54268f3"><W3CDTF xmlns="http://purl.org/dc/terms/" xml:lang="en">2002-10-15T00:00:00+00:00</W3CDTF></rdf:Description><rdf:Description rdf:about="rdf:#b6f119a8-0dd4-4e9d-b28c-79074e77cd42"><rdf:value xml:lang="en">Recoded the model to remove the reaction element. The model now runs in PCEnv and COR to generate results which are close to those in the original published paper.</rdf:value><cmeta:modifier><rdf:Description rdf:about="rdf:#671acd9f-ea5e-46a9-a8d6-522b62c66e3b"/></cmeta:modifier><modified xmlns="http://purl.org/dc/terms/"><rdf:Description rdf:about="rdf:#1d7279f5-4619-442d-8b92-180283ae8599"/></modified></rdf:Description><rdf:Description rdf:about="rdf:#55d8d6ef-7fda-43f3-8816-e1e09668416c"><rdf:_6 xml:lang="en">t-cell</rdf:_6><rdf:_5 xml:lang="en">interleukin-2</rdf:_5><rdf:type><rdf:Description rdf:about="http://www.w3.org/1999/02/22-rdf-syntax-ns#Bag"/></rdf:type><rdf:_1 xml:lang="en">pharmacodynamics</rdf:_1><rdf:_2 xml:lang="en">immunology</rdf:_2><rdf:_4 xml:lang="en">IL-2</rdf:_4><rdf:_3 xml:lang="en">signal transduction</rdf:_3><rdf:_8 xml:lang="en">T cell</rdf:_8><rdf:_7 xml:lang="en">il-2</rdf:_7></rdf:Description><rdf:Description rdf:about="rdf:#967cfc85-8837-45df-9bd3-82eebeea8c01"><rdf:type><rdf:Description rdf:about="http://www.cellml.org/bqs/1.0#Person"/></rdf:type><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#c81c4d97-3f57-41c0-a37a-43ffa8960056"/></N></rdf:Description><rdf:Description rdf:nodeID="n2"><maximumStepSize xmlns="http://www.cellml.org/metadata/simulation/1.0#" xml:lang="en">100</maximumStepSize><endingValue xmlns="http://www.cellml.org/metadata/simulation/1.0#" xml:lang="en">8000</endingValue></rdf:Description><rdf:Description rdf:about="rdf:#c81c4d97-3f57-41c0-a37a-43ffa8960056"><Other xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">A</Other><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Douglas</Given><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Lauffenburger</Family></rdf:Description><rdf:Description rdf:about="rdf:#3a1a5b6f-da95-4d60-a4b8-1d4f5901007c"><W3CDTF xmlns="http://purl.org/dc/terms/" xml:lang="en">2003-04-09</W3CDTF></rdf:Description><rdf:Description rdf:nodeID="n3"><boundIntervals xmlns="http://www.cellml.org/metadata/simulation/1.0#"><rdf:Description rdf:nodeID="n1"/></boundIntervals></rdf:Description><rdf:Description rdf:about="rdf:#a2389a96-a263-4cd8-9259-aa2716084f34"><rdf:value><rdf:Description rdf:about="rdf:#55d8d6ef-7fda-43f3-8816-e1e09668416c"/></rdf:value><subject_type xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">keyword</subject_type></rdf:Description><rdf:Description rdf:about="rdf:#b644be24-2643-4b75-8362-c68a12d52199"><FN xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Catherine Lloyd</FN></rdf:Description><rdf:Description rdf:about="rdf:#77d2f20d-ed49-4325-9474-ef7e6935396e"><Other xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">May</Other><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Catherine</Given><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Lloyd</Family></rdf:Description><rdf:Description rdf:about="Ci"><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">intracellular ligand-receptor complex</alternative><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Ci</title></rdf:Description><rdf:Description rdf:about="Cs"><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">cell surface ligand-receptor complex</alternative><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Cs</title></rdf:Description><rdf:Description rdf:about="Li"><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">intracellular IL-2 ligand</alternative><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Li</title></rdf:Description><rdf:Description rdf:about="rdf:#17ca8ca7-45d7-4b65-b74a-0ce0393f210d"><rdf:value xml:lang="en">
Added publication date information.
</rdf:value><cmeta:modifier><rdf:Description rdf:about="rdf:#7bfe4df1-345e-480c-b615-376eea2d8c3c"/></cmeta:modifier><modified xmlns="http://purl.org/dc/terms/"><rdf:Description rdf:about="rdf:#3a1a5b6f-da95-4d60-a4b8-1d4f5901007c"/></modified></rdf:Description><rdf:Description rdf:about="#fallon_lauffenburger_2000"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">
Fallon and Lauffenburger's 2000 model of the effects of ligand-receptor
binding properties on interleukin-2 trafficking dynamics and T cell
proliferation response.
</title><cmeta:comment><rdf:Description rdf:about="rdf:#16619619-4f05-442c-b41b-2f984451c437"/></cmeta:comment><simulation xmlns="http://www.cellml.org/metadata/simulation/1.0#"><rdf:Description rdf:nodeID="n3"/></simulation><reference xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:about="rdf:#5f0fdf18-d949-4855-89c8-5afe7e29c5d3"/></reference><reference xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:about="rdf:#2562b3cd-d529-43a3-befa-8aea0bbe56f9"/></reference></rdf:Description><rdf:Description rdf:about="rdf:#5157af12-c4cc-47bb-af76-10f9482bc215"><rdf:value xml:lang="en">c.lloyd@auckland.ac.nz</rdf:value><rdf:type><rdf:Description rdf:about="http://imc.org/vCard/3.0#internet"/></rdf:type></rdf:Description><rdf:Description rdf:about="rdf:#4ef8fd72-4332-447d-b06a-eae32d761543"><rdf:value xml:lang="en">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.</rdf:value><creator xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:about="rdf:#8da5fc98-677c-40bb-8d03-df54c3f9856b"/></creator></rdf:Description><rdf:Description rdf:about="L"><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">extracellular IL-2 ligand</alternative><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">L</title></rdf:Description><rdf:Description rdf:about="rdf:#d418202a-81d1-466b-aaf7-0087afa526a7"><EMAIL xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#5157af12-c4cc-47bb-af76-10f9482bc215"/></EMAIL><ORG xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#0ef470ea-1815-4857-949d-acaedee73d25"/></ORG><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#6490193c-e115-4e50-a830-abfb9d3511c8"/></N></rdf:Description><rdf:Description rdf:about="Ld"><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">degraded IL-2 ligand</alternative><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Ld</title></rdf:Description><rdf:Description rdf:about=""><publisher xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">The University of Auckland, Bioengineering Institute</publisher><created xmlns="http://purl.org/dc/terms/"><rdf:Description rdf:about="rdf:#157e07e3-4e6d-4039-9a0e-39f8d54268f3"/></created><creator xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:about="rdf:#d418202a-81d1-466b-aaf7-0087afa526a7"/></creator><cmeta:comment><rdf:Description rdf:about="rdf:#4ef8fd72-4332-447d-b06a-eae32d761543"/></cmeta:comment><cmeta:modification><rdf:Description rdf:about="rdf:#17ca8ca7-45d7-4b65-b74a-0ce0393f210d"/></cmeta:modification><cmeta:modification><rdf:Description rdf:about="rdf:#b6f119a8-0dd4-4e9d-b28c-79074e77cd42"/></cmeta:modification></rdf:Description><rdf:Description rdf:about="rdf:#2562b3cd-d529-43a3-befa-8aea0bbe56f9"><subject xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:about="rdf:#a2389a96-a263-4cd8-9259-aa2716084f34"/></subject></rdf:Description><rdf:Description rdf:about="rdf:#990c09ff-b3ac-4074-95cc-8044bcb735b5"><rdf:type><rdf:Description rdf:about="http://www.cellml.org/bqs/1.0#Person"/></rdf:type><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#4771b950-cf5b-47f6-a7a7-c3850eae0720"/></N></rdf:Description><rdf:Description rdf:about="rdf:#56370779-e2ff-4c0f-b287-87967212ff39"><W3CDTF xmlns="http://purl.org/dc/terms/" xml:lang="en">2000-09</W3CDTF></rdf:Description><rdf:Description rdf:about="rdf:#1c28ecef-57c7-4dba-9912-dbda943ee013"><last_page xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">916</last_page><issued xmlns="http://purl.org/dc/terms/"><rdf:Description rdf:about="rdf:#56370779-e2ff-4c0f-b287-87967212ff39"/></issued><creator xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:about="rdf:#cc118e82-0b3d-4266-9cb0-eabbe16ea6e9"/></creator><Journal xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:about="rdf:#b1f2bbf3-0f6d-43ed-809a-2b53518a8715"/></Journal><volume xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">16</volume><first_page xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">905</first_page><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Computational Model for Effects of Ligand/Receptor Binding
Properties on Interleukin-2 Trafficking Dynamics and T Cell
Proliferation Response</title></rdf:Description><rdf:Description rdf:about="Rs"><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">cell surface IL-2 receptor</alternative><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Rs</title></rdf:Description><rdf:Description rdf:about="rdf:#b1f2bbf3-0f6d-43ed-809a-2b53518a8715"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Biotechnology Progress</title></rdf:Description><rdf:Description rdf:about="rdf:#4771b950-cf5b-47f6-a7a7-c3850eae0720"><Other xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">M</Other><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Eric</Given><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Fallon</Family></rdf:Description><rdf:Description rdf:about="Y"><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">cell density</alternative><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Y</title></rdf:Description><rdf:Description rdf:about="rdf:#1d7279f5-4619-442d-8b92-180283ae8599"><W3CDTF xmlns="http://purl.org/dc/terms/" xml:lang="en">2008-01-01T14:41:04+13:00</W3CDTF></rdf:Description><rdf:Description rdf:about="rdf:#7bfe4df1-345e-480c-b615-376eea2d8c3c"><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#90819d10-f748-4d4a-b133-20b3723ea5f7"/></N></rdf:Description></rdf:RDF></model>
