Negative regulation of T cell activation and autoimmunity by the transmembrane adaptor protein LAB.

Journal Article (Journal Article)

LAB (linker for activation of B cells), also known as NTAL (non-T cell activation linker), is a LAT (linker for activation of T cells)-like adaptor protein that is expressed in B, NK, and mast cells. Its role in lymphocytes has not been clearly demonstrated. Here, we showed that aged LAB-deficient (Lat2(-/-)) mice developed an autoimmune syndrome. Lat2(-/-) T cells were hyperactivated and produced more cytokines than Lat2(+/+) T cells. Even though LAB was absent in naive T cells, LAB could be detected in activated Lat2(+/+) T cells. LAT-mediated signaling events were enhanced in Lat2(-/-) T cells; however, they were suppressed in T cells that overexpressed LAB. Mice with the Lat2 gene conditionally deleted from T cells also developed the autoimmune syndrome like Lat2(-/-) mice. Together, these data demonstrated an important role of LAB in limiting autoimmune response and exposed a mechanism regulating T cell activation.

Full Text

Duke Authors

Cited Authors

  • Zhu, M; Koonpaew, S; Liu, Y; Shen, S; Denning, T; Dzhagalov, I; Rhee, I; Zhang, W

Published Date

  • November 2006

Published In

Volume / Issue

  • 25 / 5

Start / End Page

  • 757 - 768

PubMed ID

  • 17081783

International Standard Serial Number (ISSN)

  • 1074-7613

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2006.08.025


  • eng

Conference Location

  • United States