Accessory molecules are thought to provide essential regulatory signals for T cell activation. In order to identify specific Intracellular events linked to triggering through accessory surface receptors, mAbs against CD2, CD3, CD4, and CD8 were employed to activate resting human T lymphocytes in vitro. Subsequently, Intracellular phosphorylation of phosphoproteln (pp) 19, a recently identified substrate of a serine phosphatase involved In CD2 mediated T cell triggering, as well as functional parameters (responsiveness to IL-6, production of IL-2 and IFN-γ) were determined. As in responses to CD2 mAbs, cross-linking of CD4 and/or CD8 to the TCR-CD3 complex but not CD3 cross-linking alone promoted pp19 dephosphorylation. This early event was in all cases followed by particular late functional responses, i.e. Induction of IL-6 responsiveness and secretion of IL-2. In marked contrast, no relationship was found between pp19 dephosphorylation and IFN-γ production. Taken together, a common intracellular pathway appears to exist In which signals mediated through CD2, CD4, and CD8 merge to promote monoklne responsiveness and IL-2 production in human T cells. Dephosphorylation of pp19 thus appears to represent a process which Is linked to critical ‘second signals’ involved in the generation of antigen Induced T cell responses.