Differential trafficking of ligands trogocytosed via CD28 versus CTLA4 promotes collective cellular control of co-stimulation

Autores
Zenke, Simon; Sica, Mauricio Pablo; Steinberg, Florian; Braun, Julia; Zink, Alicia; Gavrilov, Alina; Hilger, Alexander; Arra, Aditya; Brunner Weinzierl, Monika; Elling, Roland; Beyersdorf, Niklas; Lämmermann, Tim; Smulski, Cristian Roberto; Rohr, Jan C.
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Intercellular communication is crucial for collective regulation of cellular behaviors. While clustering T cells have been shown to mutually control the production of key communication signals, it is unclear whether they also jointly regulate their availability and degradation. Here we use newly developed reporter systems, bioinformatic analyses, protein structure modeling and genetic perturbations to assess this. We find that T cells utilize trogocytosis by competing antagonistic receptors to differentially control the abundance of immunoregulatory ligands. Specifically, ligands trogocytosed via CD28 are shuttled to the T cell surface, enabling them to co-stimulate neighboring T cells. In contrast, CTLA4-mediated trogocytosis targets ligands for degradation. Mechanistically, this fate separation is controlled by different acid-sensitivities of receptor-ligand interactions and by the receptor intracellular domains. The ability of CD28 and CTLA4 to confer different fates to trogocytosed ligands reveals an additional layer of collective regulation of cellular behaviors and promotes the robustness of population dynamics.
Fil: Zenke, Simon. Albert Ludwigs University of Freiburg; Alemania
Fil: Sica, Mauricio Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Steinberg, Florian. Albert Ludwigs University of Freiburg; Alemania
Fil: Braun, Julia. Albert Ludwigs University of Freiburg; Alemania
Fil: Zink, Alicia. Albert Ludwigs University of Freiburg; Alemania
Fil: Gavrilov, Alina. Max Planck Institute of Immunobiology and Epigenetics; Alemania
Fil: Hilger, Alexander. Albert Ludwigs University of Freiburg; Alemania
Fil: Arra, Aditya. Otto-von-Guericke-Universität Magdeburg; Alemania
Fil: Brunner Weinzierl, Monika. Otto-von-Guericke-Universität Magdeburg; Alemania
Fil: Elling, Roland. Albert Ludwigs University of Freiburg; Alemania
Fil: Beyersdorf, Niklas. Universität Würzburg; Alemania
Fil: Lämmermann, Tim. Albert Ludwigs University of Freiburg; Alemania
Fil: Smulski, Cristian Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rohr, Jan C.. Albert Ludwigs University of Freiburg; Alemania
Materia
trafficking
trogocytosis
CD28
CTLA4
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/222116
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/222116
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Differential trafficking of ligands trogocytosed via CD28 versus CTLA4 promotes collective cellular control of co-stimulationZenke, SimonSica, Mauricio PabloSteinberg, FlorianBraun, JuliaZink, AliciaGavrilov, AlinaHilger, AlexanderArra, AdityaBrunner Weinzierl, MonikaElling, RolandBeyersdorf, NiklasLämmermann, TimSmulski, Cristian RobertoRohr, Jan C.traffickingtrogocytosisCD28CTLA4https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Intercellular communication is crucial for collective regulation of cellular behaviors. While clustering T cells have been shown to mutually control the production of key communication signals, it is unclear whether they also jointly regulate their availability and degradation. Here we use newly developed reporter systems, bioinformatic analyses, protein structure modeling and genetic perturbations to assess this. We find that T cells utilize trogocytosis by competing antagonistic receptors to differentially control the abundance of immunoregulatory ligands. Specifically, ligands trogocytosed via CD28 are shuttled to the T cell surface, enabling them to co-stimulate neighboring T cells. In contrast, CTLA4-mediated trogocytosis targets ligands for degradation. Mechanistically, this fate separation is controlled by different acid-sensitivities of receptor-ligand interactions and by the receptor intracellular domains. The ability of CD28 and CTLA4 to confer different fates to trogocytosed ligands reveals an additional layer of collective regulation of cellular behaviors and promotes the robustness of population dynamics.Fil: Zenke, Simon. Albert Ludwigs University of Freiburg; AlemaniaFil: Sica, Mauricio Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Steinberg, Florian. Albert Ludwigs University of Freiburg; AlemaniaFil: Braun, Julia. Albert Ludwigs University of Freiburg; AlemaniaFil: Zink, Alicia. Albert Ludwigs University of Freiburg; AlemaniaFil: Gavrilov, Alina. Max Planck Institute of Immunobiology and Epigenetics; AlemaniaFil: Hilger, Alexander. Albert Ludwigs University of Freiburg; AlemaniaFil: Arra, Aditya. Otto-von-Guericke-Universität Magdeburg; AlemaniaFil: Brunner Weinzierl, Monika. Otto-von-Guericke-Universität Magdeburg; AlemaniaFil: Elling, Roland. Albert Ludwigs University of Freiburg; AlemaniaFil: Beyersdorf, Niklas. Universität Würzburg; AlemaniaFil: Lämmermann, Tim. Albert Ludwigs University of Freiburg; AlemaniaFil: Smulski, Cristian Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rohr, Jan C.. Albert Ludwigs University of Freiburg; AlemaniaNature2022-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/222116Zenke, Simon; Sica, Mauricio Pablo; Steinberg, Florian; Braun, Julia; Zink, Alicia; et al.; Differential trafficking of ligands trogocytosed via CD28 versus CTLA4 promotes collective cellular control of co-stimulation; Nature; Nature Communications; 13; 1; 12-2022; 1-182041-1723CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41467-022-34156-1info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:16:53Zoai:ri.conicet.gov.ar:11336/222116instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:16:53.738CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Differential trafficking of ligands trogocytosed via CD28 versus CTLA4 promotes collective cellular control of co-stimulation
title Differential trafficking of ligands trogocytosed via CD28 versus CTLA4 promotes collective cellular control of co-stimulation
spellingShingle Differential trafficking of ligands trogocytosed via CD28 versus CTLA4 promotes collective cellular control of co-stimulation
Zenke, Simon
trafficking
trogocytosis
CD28
CTLA4
title_short Differential trafficking of ligands trogocytosed via CD28 versus CTLA4 promotes collective cellular control of co-stimulation
title_full Differential trafficking of ligands trogocytosed via CD28 versus CTLA4 promotes collective cellular control of co-stimulation
title_fullStr Differential trafficking of ligands trogocytosed via CD28 versus CTLA4 promotes collective cellular control of co-stimulation
title_full_unstemmed Differential trafficking of ligands trogocytosed via CD28 versus CTLA4 promotes collective cellular control of co-stimulation
title_sort Differential trafficking of ligands trogocytosed via CD28 versus CTLA4 promotes collective cellular control of co-stimulation
dc.creator.none.fl_str_mv Zenke, Simon
Sica, Mauricio Pablo
Steinberg, Florian
Braun, Julia
Zink, Alicia
Gavrilov, Alina
Hilger, Alexander
Arra, Aditya
Brunner Weinzierl, Monika
Elling, Roland
Beyersdorf, Niklas
Lämmermann, Tim
Smulski, Cristian Roberto
Rohr, Jan C.
author Zenke, Simon
author_facet Zenke, Simon
Sica, Mauricio Pablo
Steinberg, Florian
Braun, Julia
Zink, Alicia
Gavrilov, Alina
Hilger, Alexander
Arra, Aditya
Brunner Weinzierl, Monika
Elling, Roland
Beyersdorf, Niklas
Lämmermann, Tim
Smulski, Cristian Roberto
Rohr, Jan C.
author_role author
author2 Sica, Mauricio Pablo
Steinberg, Florian
Braun, Julia
Zink, Alicia
Gavrilov, Alina
Hilger, Alexander
Arra, Aditya
Brunner Weinzierl, Monika
Elling, Roland
Beyersdorf, Niklas
Lämmermann, Tim
Smulski, Cristian Roberto
Rohr, Jan C.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv trafficking
trogocytosis
CD28
CTLA4
topic trafficking
trogocytosis
CD28
CTLA4
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Intercellular communication is crucial for collective regulation of cellular behaviors. While clustering T cells have been shown to mutually control the production of key communication signals, it is unclear whether they also jointly regulate their availability and degradation. Here we use newly developed reporter systems, bioinformatic analyses, protein structure modeling and genetic perturbations to assess this. We find that T cells utilize trogocytosis by competing antagonistic receptors to differentially control the abundance of immunoregulatory ligands. Specifically, ligands trogocytosed via CD28 are shuttled to the T cell surface, enabling them to co-stimulate neighboring T cells. In contrast, CTLA4-mediated trogocytosis targets ligands for degradation. Mechanistically, this fate separation is controlled by different acid-sensitivities of receptor-ligand interactions and by the receptor intracellular domains. The ability of CD28 and CTLA4 to confer different fates to trogocytosed ligands reveals an additional layer of collective regulation of cellular behaviors and promotes the robustness of population dynamics.
Fil: Zenke, Simon. Albert Ludwigs University of Freiburg; Alemania
Fil: Sica, Mauricio Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Steinberg, Florian. Albert Ludwigs University of Freiburg; Alemania
Fil: Braun, Julia. Albert Ludwigs University of Freiburg; Alemania
Fil: Zink, Alicia. Albert Ludwigs University of Freiburg; Alemania
Fil: Gavrilov, Alina. Max Planck Institute of Immunobiology and Epigenetics; Alemania
Fil: Hilger, Alexander. Albert Ludwigs University of Freiburg; Alemania
Fil: Arra, Aditya. Otto-von-Guericke-Universität Magdeburg; Alemania
Fil: Brunner Weinzierl, Monika. Otto-von-Guericke-Universität Magdeburg; Alemania
Fil: Elling, Roland. Albert Ludwigs University of Freiburg; Alemania
Fil: Beyersdorf, Niklas. Universität Würzburg; Alemania
Fil: Lämmermann, Tim. Albert Ludwigs University of Freiburg; Alemania
Fil: Smulski, Cristian Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rohr, Jan C.. Albert Ludwigs University of Freiburg; Alemania
description Intercellular communication is crucial for collective regulation of cellular behaviors. While clustering T cells have been shown to mutually control the production of key communication signals, it is unclear whether they also jointly regulate their availability and degradation. Here we use newly developed reporter systems, bioinformatic analyses, protein structure modeling and genetic perturbations to assess this. We find that T cells utilize trogocytosis by competing antagonistic receptors to differentially control the abundance of immunoregulatory ligands. Specifically, ligands trogocytosed via CD28 are shuttled to the T cell surface, enabling them to co-stimulate neighboring T cells. In contrast, CTLA4-mediated trogocytosis targets ligands for degradation. Mechanistically, this fate separation is controlled by different acid-sensitivities of receptor-ligand interactions and by the receptor intracellular domains. The ability of CD28 and CTLA4 to confer different fates to trogocytosed ligands reveals an additional layer of collective regulation of cellular behaviors and promotes the robustness of population dynamics.
publishDate 2022
dc.date.none.fl_str_mv 2022-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/222116
Zenke, Simon; Sica, Mauricio Pablo; Steinberg, Florian; Braun, Julia; Zink, Alicia; et al.; Differential trafficking of ligands trogocytosed via CD28 versus CTLA4 promotes collective cellular control of co-stimulation; Nature; Nature Communications; 13; 1; 12-2022; 1-18
2041-1723
CONICET Digital
CONICET
url http://hdl.handle.net/11336/222116
identifier_str_mv Zenke, Simon; Sica, Mauricio Pablo; Steinberg, Florian; Braun, Julia; Zink, Alicia; et al.; Differential trafficking of ligands trogocytosed via CD28 versus CTLA4 promotes collective cellular control of co-stimulation; Nature; Nature Communications; 13; 1; 12-2022; 1-18
2041-1723
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/s41467-022-34156-1
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature
publisher.none.fl_str_mv Nature
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.993085

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