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http://hdl.handle.net/10261/153158
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dc.contributor.author | Castro, Mario | - |
dc.contributor.author | Santen, Hisse M. van | - |
dc.contributor.author | Férez, María | - |
dc.contributor.author | Alarcón, Balbino | - |
dc.contributor.author | Lythe, Grant | - |
dc.contributor.author | Molina-Paris, C. | - |
dc.date.accessioned | 2017-07-14T12:32:35Z | - |
dc.date.available | 2017-07-14T12:32:35Z | - |
dc.date.issued | 2014-04-30 | - |
dc.identifier.citation | Frontiers in Immunology 5: 132 (2014) | - |
dc.identifier.issn | 1664-3224 | - |
dc.identifier.uri | http://hdl.handle.net/10261/153158 | - |
dc.description.abstract | T cell activation, initiated by T cell receptor (TCR) mediated recognition of pathogen-derived peptides presented by major histocompatibility complex class I or II molecules (pMHC), shows exquisite specificity and sensitivity, even though the TCR–pMHC binding interaction is of low affinity. Recent experimental work suggests that TCR pre-clustering may be a mechanism via which T cells can achieve such high sensitivity. The unresolved stoichiometry of the TCR makes TCR–pMHC binding and TCR triggering, an open question. We formulate a mathematical model to characterize the pre-clustering of T cell receptors (TCRs) on the surface of T cells, motivated by the experimentally observed distribution of TCR clusters on the surface of naive and memory T cells. We extend a recently introduced stochastic criterion to compute the timescales of T cell responses, assuming that ligand-induced cross-linked TCR is the minimum signaling unit. We derive an approximate formula for the mean time to signal initiation. Our results show that pre-clustering reduces the mean activation time. However, additional mechanisms favoring the existence of clusters are required to explain the difference between naive and memory T cell responses. We discuss the biological implications of our results, and both the compatibility and complementarity of our approach with other existing mathematical models. | - |
dc.description.sponsorship | This work has been partially supported through Grants No. FIS2009-12964-C05-03 (Mario Castro, Grant Lythe, Carmen Molina-París), BFU2009-08009 from the Ministerio de Ciencia e Innovación (Hisse M. van Santen), FP7 PIRSES-GA-2008-230665 and PIRSES-GA-2012-317893 (Mario Castro, Grant Lythe, and Carmen Molina-París), BBSRC BB/F003811/1 (Grant Lythe and Carmen Molina-París), and BBSRC BB/G023395/1 (Carmen Molina-París). | - |
dc.publisher | Frontiers Media | - |
dc.relation | info:eu-repo/grantAgreement/EC/FP7/230665 | - |
dc.relation.isversionof | Publisher's version | - |
dc.rights | openAccess | - |
dc.title | Receptor Pre-Clustering and T cell Responses: Insights into Molecular Mechanisms | - |
dc.type | artículo | - |
dc.identifier.doi | 10.3389/fimmu.2014.00132 | - |
dc.description.peerreviewed | Peer reviewed | - |
dc.relation.publisherversion | http://dx.doi.org/10.3389/fimmu.2014.00132 | - |
dc.date.updated | 2017-07-14T12:32:35Z | - |
dc.description.version | Peer Reviewed | - |
dc.language.rfc3066 | en | - |
dc.rights.holder | Copyright © 2014 Castro, van Santen, Férez, Alarcón, Lythe and Molina-París. | - |
dc.rights.license | http://creativecommons.org/licenses/by/4.0/ | - |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | - |
dc.contributor.funder | European Commission | - |
dc.relation.csic | Sí | - |
dc.identifier.funder | http://dx.doi.org/10.13039/501100000780 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100004837 | es_ES |
dc.identifier.pmid | 24817867 | - |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.cerifentitytype | Publications | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.grantfulltext | open | - |
item.openairetype | artículo | - |
item.fulltext | With Fulltext | - |
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Receptor_Pre-Clustering.pdf | 1,58 MB | Adobe PDF | Visualizar/Abrir |
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