| First Author | Lutes LK | Year | 2021 |
| Journal | Elife | Volume | 10 |
| PubMed ID | 33884954 | Mgi Jnum | J:343921 |
| Mgi Id | MGI:6728642 | Doi | 10.7554/eLife.65435 |
| Citation | Lutes LK, et al. (2021) T cell self-reactivity during thymic development dictates the timing of positive selection. Elife 10:e65435 |
| abstractText | Functional tuning of T cells based on their degree of self-reactivity is established during positive selection in the thymus, although how positive selection differs for thymocytes with relatively low versus high self-reactivity is unclear. In addition, preselection thymocytes are highly sensitive to low-affinity ligands, but the mechanism underlying their enhanced T cell receptor (TCR) sensitivity is not fully understood. Here we show that murine thymocytes with low self-reactivity experience briefer TCR signals and complete positive selection more slowly than those with high self-reactivity. Additionally, we provide evidence that cells with low self-reactivity retain a preselection gene expression signature as they mature, including genes previously implicated in modulating TCR sensitivity and a novel group of ion channel genes. Our results imply that thymocytes with low self-reactivity downregulate TCR sensitivity more slowly during positive selection, and associate membrane ion channel expression with thymocyte self-reactivity and progress through positive selection. |
