| First Author | Bovolenta ER | Year | 2022 |
| Journal | Proc Natl Acad Sci U S A | Volume | 119 |
| Issue | 22 | Pages | e2201907119 |
| PubMed ID | 35617435 | Mgi Jnum | J:331472 |
| Mgi Id | MGI:7388112 | Doi | 10.1073/pnas.2201907119 |
| Citation | Bovolenta ER, et al. (2022) A set point in the selection of the alphabetaTCR T cell repertoire imposed by pre-TCR signaling strength. Proc Natl Acad Sci U S A 119(22):e2201907119 |
| abstractText | 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 CD3zeta chain, we show here that the strength of pre-TCR-mediated signaling during T cell development determines the diversity of the TCRbeta repertoire available for positive and negative selection, and hence of the final alphabetaTCR repertoire. This finding uncovers an unexpected, pre-TCR signaling-dependent and repertoire-shaping role for beta-selection beyond selection of in-frame rearranged TCRbeta 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. |
