Cell
Volume 129, Issue 1, 6 April 2007, Pages 147-161
Journal home page for Cell

Article
miR-181a Is an Intrinsic Modulator of T Cell Sensitivity and Selection

https://doi.org/10.1016/j.cell.2007.03.008Get rights and content
Under an Elsevier user license
open archive

Summary

T cell sensitivity to antigen is intrinsically regulated during maturation to ensure proper development of immunity and tolerance, but how this is accomplished remains elusive. Here we show that increasing miR-181a expression in mature T cells augments the sensitivity to peptide antigens, while inhibiting miR-181a expression in the immature T cells reduces sensitivity and impairs both positive and negative selection. Moreover, quantitative regulation of T cell sensitivity by miR-181a enables mature T cells to recognize antagonists—the inhibitory peptide antigens—as agonists. These effects are in part achieved by the downregulation of multiple phosphatases, which leads to elevated steady-state levels of phosphorylated intermediates and a reduction of the T cell receptor signaling threshold. Importantly, higher miR-181a expression correlates with greater T cell sensitivity in immature T cells, suggesting that miR-181a acts as an intrinsic antigen sensitivity “rheostat” during T cell development.

Cited by (0)

8

These authors contributed equally to this work.