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dc.contributor.authorSiokis, Anastasios
dc.contributor.authorRobert, Philippe A
dc.contributor.authorMeyer-Hermann, Michael
dc.date.accessioned2020-10-08T09:03:05Z
dc.date.available2020-10-08T09:03:05Z
dc.date.issued2020-09-04
dc.identifier.citation. Int J Mol Sci. 2020 Sep 4;21(18):E6473. doi: 10.3390/ijms21186473.en_US
dc.identifier.pmid32899840
dc.identifier.doi10.3390/ijms21186473
dc.identifier.urihttp://hdl.handle.net/10033/622499
dc.description.abstractImmunological synapse (IS) formation is a key event during antigen recognition by T cells. Recent experimental evidence suggests that the affinity between T cell receptors (TCRs) and antigen is actively modulated during the early steps of TCR signaling. In this work, we used an agent-based model to study possible mechanisms for affinity modulation during IS formation. We show that, without any specific active mechanism, the observed affinity between receptors and ligands evolves over time and depends on the density of ligands of the antigen peptide presented by major histocompatibility complexes (pMHC) and TCR molecules. A comparison between the presence or absence of TCR-pMHC centrally directed flow due to F-actin coupling suggests that centripetal transport is a potential mechanism for affinity modulation. The model further suggests that the time point of affinity measurement during immune synapse formation is critical. Finally, a mathematical model of F-actin foci formation incorporated in the agent-based model shows that TCR affinity can potentially be actively modulated by positive/negative feedback of the F-actin foci on the TCR-pMHC association rate kon.en_US
dc.language.isoenen_US
dc.publisherMDPIen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectF-actin focien_US
dc.subjectTCR cooperativityen_US
dc.subjectagent-based modelingen_US
dc.subjectimmunological synapseen_US
dc.titleAgent-Based Modeling of T Cell Receptor Cooperativity.en_US
dc.typeArticleen_US
dc.identifier.eissn1422-0067
dc.contributor.departmentBRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.en_US
dc.identifier.journalInternational journal of molecular sciencesen_US
dc.source.volume21
dc.source.issue18
refterms.dateFOA2020-10-08T09:03:06Z
dc.source.journaltitleInternational journal of molecular sciences
dc.source.countrySwitzerland


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Attribution-NonCommercial-ShareAlike 4.0 International
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