DISTINCT BIOCHEMICAL SIGNALS CHARACTERIZE AGONIST-INDUCED AND ALTEREDPEPTIDE LIGAND-INDUCED DIFFERENTIATION OF NAIVE CD4(-CELLS INTO TH1 AND TH2 SUBSETS() T)

We have recently shown that altered peptide ligands influence differen tiation of CD4(+) T cells into Th1 and Th2 subsets. In the present stu dy, we have examined the biochemical signals in naive CD4(+) T cells a fter priming with altered peptide ligand (APL) that correlate with dif ferences in cytokine expression. Although we observed zeta-chain phosp horylation in APL-stimulated cells, other signaling events such as ZAP 70 and Lnk phosphorylation are not initiated. This altered pattern obs erved in the early phosphorylation events correlates with a distinct C a2+ mobilization pattern that characterizes APL-stimulated cells. By c hanging the calcium signaling environment during T cell priming, we pr esent data indicating that qualitative differences in calcium mobiliza tion are associated with differentiation of naive CD4(+) T cells into Th1- and Th2-like effector subsets.