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

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• dc.contributor.author Bovolenta, Elena R.
• dc.contributor.author García-Cuesta, Eva M.
• dc.contributor.author Horndler, Lydia
• dc.contributor.author Ponomarenko, Julia
• dc.contributor.author Schamel, Wolfgang W.
• dc.contributor.author Mellado, Mario
• dc.contributor.author Castro, Mario
• dc.contributor.author Abia, David
• dc.contributor.author van Santen, Hisse M.
• dc.date.accessioned 2022-11-08T07:12:51Z
• dc.date.available 2022-11-08T07:12:51Z
• dc.date.issued 2022
• dc.description.abstract 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.
• dc.description.sponsorship 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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Bovolenta ER, García-Cuesta EM, Horndler L, Ponomarenko J, Schamel WW, Mellado M, Castro M, Abia D, van Santen HM. A set point in the selection of the αβTCR T cell repertoire imposed by pre-TCR signaling strength. Proc Natl Acad Sci U S A. 2022 May 31;119(22):e2201907119. DOI: 10.1073/pnas.2201907119
• dc.identifier.doi http://dx.doi.org/10.1073/pnas.2201907119
• dc.identifier.issn 0027-8424
• dc.identifier.uri http://hdl.handle.net/10230/54743
• dc.language.iso eng
• dc.publisher National Academy of Sciences
• dc.relation.ispartof Proc Natl Acad Sci U S A. 2022 May 31;119(22):e2201907119
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2013-47975-R
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-76394-R
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-104703GB-I00
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/FIS2016-78883-C2-2-P
• dc.rights © 2022 the Author(s). Published by PNAS. This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.keyword Diversity
• dc.subject.keyword pre-TCR
• dc.subject.keyword Repertoire
• dc.subject.keyword Signaling
• dc.subject.keyword β-selection
• dc.title A set point in the selection of the αβTCR T cell repertoire imposed by pre-TCR signaling strength
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion