Changes in cytokine secretion induced by altered peptide ligands of myelin basic protein peptide 85-99.

LJ Ausubel, JI Krieger, DA Hafler - Journal of immunology …, 1997 - journals.aai.org
LJ Ausubel, JI Krieger, DA Hafler
Journal of immunology (Baltimore, Md.: 1950), 1997journals.aai.org
Myelin basic protein (MBP)-specific T cells were isolated directly from peripheral blood by
stimulation either with native MBPp85-99 or altered peptide ligands (APLs) in which
substitutions of the lysine were made at position 93, a TCR contact residue. We report here
that the APL 93A could alter the cytokine profile of some autoreactive MBPp85-99 reactive T
cell clones, switching them from a Th0 phenotype secreting high concentrations of IL-4, IL-5,
and IFN-gamma into Th2 cells secreting significantly less IFN-gamma. However, in vitro …
Abstract
Myelin basic protein (MBP)-specific T cells were isolated directly from peripheral blood by stimulation either with native MBPp85-99 or altered peptide ligands (APLs) in which substitutions of the lysine were made at position 93, a TCR contact residue. We report here that the APL 93A could alter the cytokine profile of some autoreactive MBPp85-99 reactive T cell clones, switching them from a Th0 phenotype secreting high concentrations of IL-4, IL-5, and IFN-gamma into Th2 cells secreting significantly less IFN-gamma. However, in vitro stimulation with the 93A peptide, in some instances, induced T cells that responded better to the native MBPp85-99 peptide. Functionally, the APL 93A was shown to act as an antagonist for IFN-gamma secretion. Based on TCR sequencing and single cell cloning, this alteration in cytokine profile was determined to be the result of the differential activation of individual T cell clones. We discuss the implications of these data for the strength of signal model of T cell activation.
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