Lj. Ausubel et al., CHANGES IN CYTOKINE SECRETION INDUCED BY ALTERED PEPTIDE LIGANDS OF MYELIN BASIC-PROTEIN PEPTIDE-85-99, The Journal of immunology, 159(5), 1997, pp. 2502-2512
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.