CD81 controls sustained T cell activation signaling and defines the maturation stages of cognate immunological synapses

In this study, we investigated the dynamics of the molecular interactions of tetraspanin CD81 in T lymphocytes, and we show that CD81 controls the organization of the immune synapse (IS) and T cell activation. Using quantitative microscopy, including fluorescence recovery after photobleaching (FRAP)...

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Autores: Rocha Perugini, Vera, Zamai, Moreno, González Granado, José María, Barreiro, Olga, Tejera, Emilio, Yáñez Mo, María, Caiolfa, Valeria R., Sánchez Madrid, Francisco
Tipo de recurso: artículo
Fecha de publicación:2013
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/664901
Acceso en línea:http://hdl.handle.net/10486/664901
https://dx.doi.org/10.1128/MCB.00302-13
Access Level:acceso abierto
Palabra clave:CD81 antigen
Immunological Synapses
Lymphocyte Activation
Fluorescence Resonance Energy Transfer
Cell Differentiation
Medicina
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spelling CD81 controls sustained T cell activation signaling and defines the maturation stages of cognate immunological synapsesRocha Perugini, VeraZamai, MorenoGonzález Granado, José MaríaBarreiro, OlgaTejera, EmilioYáñez Mo, MaríaCaiolfa, Valeria R.Sánchez Madrid, FranciscoCD81 antigenImmunological SynapsesLymphocyte ActivationFluorescence Resonance Energy TransferCell DifferentiationMedicinaIn this study, we investigated the dynamics of the molecular interactions of tetraspanin CD81 in T lymphocytes, and we show that CD81 controls the organization of the immune synapse (IS) and T cell activation. Using quantitative microscopy, including fluorescence recovery after photobleaching (FRAP), phasor fluorescence lifetime imaging microscopy-Föster resonance energy transfer (phasorFLIM-FRET), and total internal reflection fluorescence microscopy (TIRFM), we demonstrate that CD81 interacts with ICAM-1 and CD3 during conjugation between T cells and antigen-presenting cells (APCs). CD81 and ICAM-1 exhibit distinct mobilities in central and peripheral areas of early and late T cell-APC contacts. Moreover, CD81-ICAM-1 and CD81- CD3 dynamic interactions increase over the time course of IS formation, as these molecules redistribute throughout the contact area. Therefore, CD81 associations unexpectedly define novel sequential steps of IS maturation. Our results indicate that CD81 controls the temporal progression of the IS and the permanence of CD3 in the membrane contact area, contributing to sustained T cell receptor (TCR)-CD3-mediated signaling. Accordingly, we find that CD81 is required for proper T cell activation, regulating CD3ζ, ZAP-70, LAT, and extracellular signal-regulated kinase (ERK) phosphorylation; CD69 surface expression; and interleukin- 2 (IL-2) secretion. Our data demonstrate the important role of CD81 in the molecular organization and dynamics of the IS architecture that sets the signaling threshold in T cell activationThis work was supported by SAF2011-25834 from the Spanish Ministry of Science and Innovation, INDISNET-S2011/BMD-2332 from the Comunidad de Madrid, Cardiovascular Network RD12-0042-0056 from the Instituto Salud Carlos III, and ERC-2011-AdG 294340-GENTRISAmerican Society for MicrobiologyDepartamento de MedicinaFacultad de Medicina20132013-09-11research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/664901https://dx.doi.org/10.1128/MCB.00302-13reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6649012026-06-23T12:46:27Z
dc.title.none.fl_str_mv CD81 controls sustained T cell activation signaling and defines the maturation stages of cognate immunological synapses
title CD81 controls sustained T cell activation signaling and defines the maturation stages of cognate immunological synapses
spellingShingle CD81 controls sustained T cell activation signaling and defines the maturation stages of cognate immunological synapses
Rocha Perugini, Vera
CD81 antigen
Immunological Synapses
Lymphocyte Activation
Fluorescence Resonance Energy Transfer
Cell Differentiation
Medicina
title_short CD81 controls sustained T cell activation signaling and defines the maturation stages of cognate immunological synapses
title_full CD81 controls sustained T cell activation signaling and defines the maturation stages of cognate immunological synapses
title_fullStr CD81 controls sustained T cell activation signaling and defines the maturation stages of cognate immunological synapses
title_full_unstemmed CD81 controls sustained T cell activation signaling and defines the maturation stages of cognate immunological synapses
title_sort CD81 controls sustained T cell activation signaling and defines the maturation stages of cognate immunological synapses
dc.creator.none.fl_str_mv Rocha Perugini, Vera
Zamai, Moreno
González Granado, José María
Barreiro, Olga
Tejera, Emilio
Yáñez Mo, María
Caiolfa, Valeria R.
Sánchez Madrid, Francisco
author Rocha Perugini, Vera
author_facet Rocha Perugini, Vera
Zamai, Moreno
González Granado, José María
Barreiro, Olga
Tejera, Emilio
Yáñez Mo, María
Caiolfa, Valeria R.
Sánchez Madrid, Francisco
author_role author
author2 Zamai, Moreno
González Granado, José María
Barreiro, Olga
Tejera, Emilio
Yáñez Mo, María
Caiolfa, Valeria R.
Sánchez Madrid, Francisco
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Medicina
Facultad de Medicina
dc.subject.none.fl_str_mv CD81 antigen
Immunological Synapses
Lymphocyte Activation
Fluorescence Resonance Energy Transfer
Cell Differentiation
Medicina
topic CD81 antigen
Immunological Synapses
Lymphocyte Activation
Fluorescence Resonance Energy Transfer
Cell Differentiation
Medicina
description In this study, we investigated the dynamics of the molecular interactions of tetraspanin CD81 in T lymphocytes, and we show that CD81 controls the organization of the immune synapse (IS) and T cell activation. Using quantitative microscopy, including fluorescence recovery after photobleaching (FRAP), phasor fluorescence lifetime imaging microscopy-Föster resonance energy transfer (phasorFLIM-FRET), and total internal reflection fluorescence microscopy (TIRFM), we demonstrate that CD81 interacts with ICAM-1 and CD3 during conjugation between T cells and antigen-presenting cells (APCs). CD81 and ICAM-1 exhibit distinct mobilities in central and peripheral areas of early and late T cell-APC contacts. Moreover, CD81-ICAM-1 and CD81- CD3 dynamic interactions increase over the time course of IS formation, as these molecules redistribute throughout the contact area. Therefore, CD81 associations unexpectedly define novel sequential steps of IS maturation. Our results indicate that CD81 controls the temporal progression of the IS and the permanence of CD3 in the membrane contact area, contributing to sustained T cell receptor (TCR)-CD3-mediated signaling. Accordingly, we find that CD81 is required for proper T cell activation, regulating CD3ζ, ZAP-70, LAT, and extracellular signal-regulated kinase (ERK) phosphorylation; CD69 surface expression; and interleukin- 2 (IL-2) secretion. Our data demonstrate the important role of CD81 in the molecular organization and dynamics of the IS architecture that sets the signaling threshold in T cell activation
publishDate 2013
dc.date.none.fl_str_mv 2013
2013-09-11
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/664901
https://dx.doi.org/10.1128/MCB.00302-13
url http://hdl.handle.net/10486/664901
https://dx.doi.org/10.1128/MCB.00302-13
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301629

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