CHANGES IN CYTOKINE SECRETION INDUCED BY ALTERED PEPTIDE LIGANDS OF MYELIN BASIC-PROTEIN PEPTIDE-85-99

Myelin basic protein (MBP)-specific T cells were isolated directly fro m peripheral blood by stimulation either with native MBPp85-99 or alte red peptide ligands (APLs) in which substitutions of the lysine were m ade at position 93, a TCR contact residue, We report here that the APL 93A could alter the cytokine profile of some autoreactive MBPp85-99 r eactive T cell clones, switching them from a Th0 phenotype secreting h igh concentrations of IL-4, IL-5, and IFN-gamma into Th2 cells secreti ng significantly less IFN-gamma, However, in vitro stimulation with th e 93A peptide, in some instances, induced T cells that responded bette r to the native MBPp85-99 peptide, Functionally, the APL 93A was shown to act as an antagonist for IFN-gamma secretion, Based on TCR sequenc ing and single cell cloning, this alteration in cytokine profile was d etermined to be the result of the differential activation of individua l T cell clones, We discuss the implications of these data for the str ength of signal model of T cell activation.