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 cell receptor (TCR) contact residues and bound to class II major histocompatability complex can change the cytokine pattern of mature T cell clones. Myel in basic protein peptide 85-99-reactive ThO T cell clones were stimula ted with altered peptide ligands, which acted both as TCR antagonist a nd induced new mRNA synthesis and protein secretion of TGF-beta 1, whi le no longer inducing mRNA synthesis or protein secretion of IL-2, IL- 4, IL-10, and IFN gamma. The modified peptides failed to induce a dete ctable calcium flux, p56(lck) activation, or thymidine incorporation, yet triggered nearly equal amounts of IL-4 secretion in the presence o f ionomycin. Antigen-induced modulation of T cell cytokine secretion m ay be important In regulating the immune response.