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T cell self-reactivity during thymic development dictates the timing of positive selection
oleh: Lydia K Lutes, Zoƫ Steier, Laura L McIntyre, Shraddha Pandey, James Kaminski, Ashley R Hoover, Silvia Ariotti, Aaron Streets, Nir Yosef, Ellen A Robey
Format: | Article |
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Diterbitkan: | eLife Sciences Publications Ltd 2021-04-01 |
Deskripsi
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.