THE CYTOPLASMIC DOMAIN OF CD5 MEDIATES BOTH TCR CD3-DEPENDENT AND TCR/CD3-INDEPENDENT DIACYLGLYCEROL PRODUCTION/

CD5 is a 67-kDa surface glycoprotein found in association with the Ag receptor complex on both T and B lymphocytes. CD5 modulates Ag recepto r-mediated immune responses, but the molecular mechanisms of its actio n remain unclear. In this respect, the assessment of the relative and unique contribution of CD5 in cell signaling events is a crucial point , We have used Jurkat variants and anti-CD5 mAbs to show that the CD5 signaling pathway is distinct from that used by the TCR/CD3 complex, W e hereby identify two independent mechanisms of CD5-mediated diacylgly cerol release by virtue of their different kinetics: 1) an early and t ransient diacylglycerol increase that results from the activation of a phosphatidylcholine-specific phospholipase C, and 2) a late and susta ined increase that requires de novo phospholipid synthesis, Studies pe rformed on a TCR/CD3-deficient Jurkat cell variant indicate that only the CD5-mediated phosphatidylcholine-specific phospholipase C activati on is dependent on TCR/CD3 expression, Mutational analyses of CD5 demo nstrate that both mechanisms are dependent on the integrity of the CD5 distal cytoplasmic region, Our results show that CD5 is a signaling m olecule per se that uses mechanisms resembling those used by some cyto kine receptors (such as IL-1 or TNF receptors) to modulate lymphocyte activation.