Modulation of cytokine patterns of human autoreactive T cell clones by a single amino acid substitution of their peptide ligand

We demonstrate that cognate peptide ligands altered at T call receptor (TCR) contact residues and bound to class II major histocompetability complex can change the cytokine pattern of mature T cell clones. Myelin basic protein peptide 85–99-reactive Th0 T cell clones were stimulated with altered peptide ligands, which acted both as TCR antagonist and induced new mRNA synthesis and protein secretion of TGF-β1, while no longer inducing mRNA synthesis or protein secretion of IL-2, IL-4, IL-10, and IFNγ. The modified peptides failed to induce a detectable calcium flux, p58 lck activation, or thymidine Incorporation, yet triggered nearly equal amounts of IL-4 secretion in the presence of ion-omycin. Antigen-induced modulation of T cell cytokine secretion may be important in regulating the immune response.