We demonstrate that cognate peptide llgands altered at T cell receptor (TCR) contact residues and bound to class II major histocompatablllty complex can change the cytokine pattern of mature T cell clones. Myelln basic protein peptlde 8888-reactive ThO T cell clones were stimulated wlth altered peptlde ligands, which acted both as TCR antagonist and Induced new mRNA synthesis and proteln secretion of TGF-81, while no longer inducing mRNA synthesis or protein secretlon of IL-2, IL-4, IL-lo, and IFNT. The modffied peptldes falled to induce a detectable caklum flux,~ 88” actlvation, or thymldine Incorporatlon, yet triggered nearfy equal amounts of IL-4 secretlon in the presence of ionomycin. Antigen-Induced modulation of T cell cytoklne secretion may be important In regulating the Immune response. lntroductlon

Naive T cells differentiate into distinct populations defined by their cytokine secretion pattern and regulatory function. Thl cells secrete predominantly interleukin-2 (IL-2) and interferon y (lFNy) and are involved in classic delayed-type hypersensitivity reactions, while Th2 cells, which secrete predominantly IL4 and 11-10, induce selected immunoglobulin secretion and can down-regulate Thl-mediated immune responses (Mossmann et al., 1986; Romagnani, 1994). Thus, cytokines secreted by T cells after activation qualitatively influence the nature of the immune response. Recent reports have suggested that the dominant factors determining the maturation of naive T cells into either predominantly Thl or Th2 cells are cytokines, particularly IL-12 and IFNy for Thl and IL4 for Th2 (Seder and Paul, 1994). Other factors include the dose and type of antigen, the type of antigen-presenting cell (APC), and costimulatory molecules involved in activation. Once T cells have differentiated into Thl or Th2 type T cells, they are thought to be committed to the production of a given set of lymphokines upon restimulation.