Role of LAT in the granule-mediated cytotoxicity of CD8 T cells.

Journal Article (Journal Article)

Linker for activation of T cells (LAT) is a transmembrane adaptor protein that is essential to bridge T cell receptor (TCR) engagement to downstream signaling events. The indispensable role of LAT in thymocyte development and T cell activation has been well characterized; however, the function of LAT in cytotoxic-T-lymphocyte (CTL) cytotoxicity remains unknown. We show here that LAT-deficient CTLs failed to upregulate FasL and produce gamma interferon after engagement with target cells and had impaired granule-mediated killing. We further dissected the effect of the LAT deletion on each step of granule exocytosis. LAT deficiency led to altered synapse formation, subsequently causing unstable T cell-antigen-presenting cell (APC) conjugates. Microtubule organizing center polarization and granule reorientation were also impaired by LAT deficiency, leading to reduced granule delivery. Despite these defects, granule release was still observed in LAT-deficient CTLs due to residual calcium flux and phospholipase C (PLC) activity. Our data demonstrated that LAT-mediated signaling intricately regulates CTL cytotoxicity at multiple steps.

Full Text

Duke Authors

Cited Authors

  • Ou-Yang, C-W; Zhu, M; Fuller, DM; Sullivan, SA; Chuck, MI; Ogden, S; Li, Q-J; Zhang, W

Published Date

  • July 2012

Published In

Volume / Issue

  • 32 / 14

Start / End Page

  • 2674 - 2684

PubMed ID

  • 22566687

Pubmed Central ID

  • PMC3416195

Electronic International Standard Serial Number (EISSN)

  • 1098-5549

Digital Object Identifier (DOI)

  • 10.1128/MCB.00356-12


  • eng

Conference Location

  • United States