Publication:20221021113306
From Bioinformatics Core Wiki
| Publication | |
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| URL | https://pubmed.ncbi.nlm.nih.gov/35617435/ |
| Title | A set point in the selection of the αβTCR T cell repertoire imposed by pre-TCR signaling strength
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| Authors | Elena R. Bovolenta, Eva M. García-Cuesta, Lydia Horndler, Julia Ponomarenko, Wolfgang W. Schamel, Mario Mellado, Mario Castro, David Abia, Hisse M. van Santen |
| Date | 2022-05-31
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| Publisher | Proceedings of the National Academy of Sciences of the United States of America |
| DOI | 10.1073/pnas.2201907119 |
| Tag | Animals, CD3 Complex, Cell Differentiation, Mice, Mice, Mutant Strains, Receptors, Antigen, T-Cell, alpha-beta, Signal Transduction, T-Lymphocytes, diversity, pre-TCR, repertoire, signaling, β-selection |
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.
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.
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