Co-stimulation of T cells with CD2 augments TCR-CD3-mediated activation of protein tyrosine kinase p72syk, resulting in increased tyrosine phosphorylation of adapter proteins, Shc and Cbl

Complete T cell activation requires not only the first signal via TCR- CD3engagement, but also a co-stimulatory signal through accessory receptorssuch as CD2, LFA-1 and CD28. However, the pathway of co- stimulatorysignaling through accessory receptors is incompletely understood. We reporthere that CD2 provides a co-stimulus for activation of CD3-mediatedsyk/ZAP-70 family kinase, p72Syk (Syk), in Jurkat T cells. Althoughcross-linking of CD2 alone or any combination of CD2 with LFA-1alpha,LFA-1beta or CD28 did not induce tyrosine phosphorylation of Syk,co-cross-linking of CD2 with CD3 enhanced CD3- mediated tyrosinephosphorylation of Syk. Enhancement of tyrosine phosphorylation of Syk byCD2 co-stimulation was CD2 antibody concentration-dependent, and timecourse studies showed that CD2 co- stimulation enhanced Syk tyrosinephosphorylation by 30 s and through 5 min stimulation compared with thecontrol. In vitro kinase assay revealed that co-cross-linking of CD2 withCD3 augmented Syk kinase activity using myelin basic protein as asubstrate. Furthermore, CD2 co- stimulation with CD3 resulted in enhancedtyrosine phosphorylation of adapter proteins, such as Shc and Cbl, in anantibody concentration- dependent manner. Finally, CD2 provided aco-stimulatory signals for synthesis of IL-2 in Jurkat cells andphytohemagglutinin (PHA)- activated T cells and for proliferation ofPHA-activated T cells. Taken together, these results indicate that CD2 isan important co- stimulatory receptor for CD3-mediated T cell activationand functions in concert with CD3.