Phospholipid signaling pathways triggered by the antigen receptors in T Lymphocytes

Abstract

Stimulation of T lymphocytes through the T cell receptor (TCR) elicits broad range of responses required for immune function. Although key protein components of TCR signaling have been identified, requirements for phospholipid modifying enzymes are less clear.I investigated the roles of Phospholipase D (PLD) and Sphingosine kinase (SPHK) in TCR mediated intracellular signaling and functional responses. My results show that stimulation of TCR triggers PLD and SPHK activities and that this activation is required for rise in intracellular calcium, activation of PKC, transcription factors activation, production of cytokines and cell proliferation. My data also suggest that PLD, but not SPHK, activity is required for Raf-1 activation and p44/42 MAPK phosphorylation. I also demonstrate in vivo that SPHK1 is required for T cell functional responses during elicitation of contact hypersensitivity. Overall, my results show a pivotal role for PLD and SPHK in TCR mediated intracellular signaling cascades and functional responses.