期刊
出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2201907119
关键词
pre-TCR; signaling; diversity; repertoire; beta-selection
资金
- Formacion de Personal Investigador (FPI) fellowship [BES-2014-068000]
- European Molecular Biology Organization [7272]
- Spanish Ministry of Economy and Competitiveness (MINECO) [SAF2013-47975-R, SAF2016-76394-R]
- Spanish Ministry of Science and Innovation (MICINN) [PID2019-104703GB-I00/AEI/10.13039/501100011033, FIS2016-78883-C2-2-P]
- German Research Foundation (DFG) [BIOSS-EXC294, CIBSS-EXC2189, SFB854, FOR2799, SCHA976/8-1, SFB1381]
- Spanish Ministry of Economy and Competitiveness, Centro de Excelencia Severo Ochoa
- Centres de Recerca de Catalunya Program/Generalitat de Catalunya
- Fundacion Ramon Areces
Signaling through T cell receptor (TCR) plays a critical role in the development, maintenance, and activation of T cells. This study reveals that the strength of pre-TCR-mediated signaling during T cell development determines the diversity of TCR beta repertoire for positive and negative selection.
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 CD3. chain, we show here that the strength of pre-TCR-mediated signaling during T cell development determines the diversity of the TCR beta repertoire available for positive and negative selection, and hence of the final alpha beta TCR repertoire. This finding uncovers an unexpected, pre-TCR signaling-dependent and repertoire-shaping role for beta-selection beyond selection of in-frame rearranged TCR beta 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.
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