A set point in the selection of the αβTCR T cell repertoire imposed by pre-TCR signaling strength

Signaling via the T cell receptor (TCR) is critical during the development, maintenance, and activation of T cells. Quantitative aspects of TCR signaling have an important role during positive and negative selection, lineage choice, and ability to respond to small amounts of antigen. By using a muta...

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Detalles Bibliográficos
Autores: Bovolenta, Elena R., García-Cuesta, Eva M., Horndler, Lydia, Ponomarenko, Julia, Schamel, Wolfgang W., Mellado, Mario, Castro, Mario, Abia, David, van Santen, Hisse M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/54743
Acceso en línea:http://hdl.handle.net/10230/54743
http://dx.doi.org/10.1073/pnas.2201907119
Access Level:acceso abierto
Palabra clave:Diversity
pre-TCR
Repertoire
Signaling
β-selection
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spelling A set point in the selection of the αβTCR T cell repertoire imposed by pre-TCR signaling strengthBovolenta, Elena R.García-Cuesta, Eva M.Horndler, LydiaPonomarenko, JuliaSchamel, Wolfgang W.Mellado, MarioCastro, MarioAbia, Davidvan Santen, Hisse M.Diversitypre-TCRRepertoireSignalingβ-selectionSignaling via the T cell receptor (TCR) is critical during the development, maintenance, and activation of T cells. Quantitative aspects of TCR signaling have an important role during positive and negative selection, lineage choice, and ability to respond to small amounts of antigen. By using a mutant mouse line expressing a hypomorphic allele of the CD3ζ chain, we show here that the strength of pre-TCR–mediated signaling during T cell development determines the diversity of the TCRβ repertoire available for positive and negative selection, and hence of the final αβTCR repertoire. This finding uncovers an unexpected, pre-TCR signaling–dependent and repertoire–shaping role for β-selection beyond selection of in-frame rearranged TCRβ chains. Our data furthermore support a model of pre-TCR signaling in which the arrangement of this receptor in stable nanoclusters determines its quantitative signaling capacity.This work was supported by Spanish Ministry of Economy and Competitiveness (MINECO) Grants SAF2013-47975-R and SAF2016-76394-R and Grant PID2019-104703GB-I00/AEI/10.13039/501100011033 from the Spanish Ministry of Science and Innovation (MICINN) (to H.M.v.S.) and FIS2016-78883-C2-2-P (to M.C.). W.W.S. was supported by the German Research Foundation (DFG) through BIOSS-EXC294 and CIBSS-EXC2189, SFB854 (B19), FOR2799 (SCHA976/8-1), and SFB1381 (A9). The Centre for Genomic Regulation acknowledges support of the Spanish Ministry of Economy and Competitiveness, “Centro de Excelencia Severo Ochoa,” and the Centres de Recerca de Catalunya Program/Generalitat de Catalunya. The Centro Biología Molecular Severo Ochoa has been supported by the Fundación Ramón Areces.National Academy of Sciences202220222022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/54743http://dx.doi.org/10.1073/pnas.2201907119reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésProc Natl Acad Sci U S A. 2022 May 31;119(22):e2201907119info:eu-repo/grantAgreement/ES/1PE/SAF2013-47975-Rinfo:eu-repo/grantAgreement/ES/1PE/SAF2016-76394-Rinfo:eu-repo/grantAgreement/ES/2PE/PID2019-104703GB-I00info:eu-repo/grantAgreement/ES/1PE/FIS2016-78883-C2-2-P© 2022 the Author(s). Published by PNAS. This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/547432026-05-29T05:05:01Z
dc.title.none.fl_str_mv A set point in the selection of the αβTCR T cell repertoire imposed by pre-TCR signaling strength
title A set point in the selection of the αβTCR T cell repertoire imposed by pre-TCR signaling strength
spellingShingle A set point in the selection of the αβTCR T cell repertoire imposed by pre-TCR signaling strength
Bovolenta, Elena R.
Diversity
pre-TCR
Repertoire
Signaling
β-selection
title_short A set point in the selection of the αβTCR T cell repertoire imposed by pre-TCR signaling strength
title_full A set point in the selection of the αβTCR T cell repertoire imposed by pre-TCR signaling strength
title_fullStr A set point in the selection of the αβTCR T cell repertoire imposed by pre-TCR signaling strength
title_full_unstemmed A set point in the selection of the αβTCR T cell repertoire imposed by pre-TCR signaling strength
title_sort A set point in the selection of the αβTCR T cell repertoire imposed by pre-TCR signaling strength
dc.creator.none.fl_str_mv Bovolenta, Elena R.
García-Cuesta, Eva M.
Horndler, Lydia
Ponomarenko, Julia
Schamel, Wolfgang W.
Mellado, Mario
Castro, Mario
Abia, David
van Santen, Hisse M.
author Bovolenta, Elena R.
author_facet Bovolenta, Elena R.
García-Cuesta, Eva M.
Horndler, Lydia
Ponomarenko, Julia
Schamel, Wolfgang W.
Mellado, Mario
Castro, Mario
Abia, David
van Santen, Hisse M.
author_role author
author2 García-Cuesta, Eva M.
Horndler, Lydia
Ponomarenko, Julia
Schamel, Wolfgang W.
Mellado, Mario
Castro, Mario
Abia, David
van Santen, Hisse M.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Diversity
pre-TCR
Repertoire
Signaling
β-selection
topic Diversity
pre-TCR
Repertoire
Signaling
β-selection
description Signaling via the T cell receptor (TCR) is critical during the development, maintenance, and activation of T cells. Quantitative aspects of TCR signaling have an important role during positive and negative selection, lineage choice, and ability to respond to small amounts of antigen. By using a mutant mouse line expressing a hypomorphic allele of the CD3ζ chain, we show here that the strength of pre-TCR–mediated signaling during T cell development determines the diversity of the TCRβ repertoire available for positive and negative selection, and hence of the final αβTCR repertoire. This finding uncovers an unexpected, pre-TCR signaling–dependent and repertoire–shaping role for β-selection beyond selection of in-frame rearranged TCRβ chains. Our data furthermore support a model of pre-TCR signaling in which the arrangement of this receptor in stable nanoclusters determines its quantitative signaling capacity.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/54743
http://dx.doi.org/10.1073/pnas.2201907119
url http://hdl.handle.net/10230/54743
http://dx.doi.org/10.1073/pnas.2201907119
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Proc Natl Acad Sci U S A. 2022 May 31;119(22):e2201907119
info:eu-repo/grantAgreement/ES/1PE/SAF2013-47975-R
info:eu-repo/grantAgreement/ES/1PE/SAF2016-76394-R
info:eu-repo/grantAgreement/ES/2PE/PID2019-104703GB-I00
info:eu-repo/grantAgreement/ES/1PE/FIS2016-78883-C2-2-P
dc.rights.none.fl_str_mv https://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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