miR-181a is an intrinsic modulator of T cell sensitivity and selection.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Li, Q-J; Chau, J; Ebert, PJR; Sylvester, G; Min, H; Liu, G; Braich, R; Manoharan, M; Soutschek, J; Skare, P; Klein, LO; Davis, MM; Chen, C-Z

Published Date

  • April 6, 2007

Published In

Volume / Issue

  • 129 / 1

Start / End Page

  • 147 - 161

PubMed ID

  • 17382377

Pubmed Central ID

  • 17382377

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2007.03.008

Language

  • eng

Conference Location

  • United States