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Center for Immunology and Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110
We examined the role of the peptide/MHC ligand in CD4+
T cell differentiation into Th1 or Th2 cells using a TCR 
ß
transgenic mouse specific for hemoglobin (Hb)(64-76)/I-Ek.
We identified two altered peptide ligands of Hb(64-76) that retain
strong agonist activity but, at a given dose, induce cytokine patterns
distinct from the Hb(64-76) peptide. The ability of these peptides to
produce distinct cytokine patterns at identical doses is not due to an
intrinsic qualitative property. Each peptide can induce Th2 cytokines
at low concentrations and Th1 cytokines at high concentrations and has
a unique range of concentrations at which these distinct effects occur.
The pattern of cytokines produced from limiting dilution of naive T
cells demonstrated that the potential to develop an individual Th1 or
Th2 cell is stochastic, independent of Ag dose. We propose that the
basis for the observed effects on the Th1/Th2 balance shown by the
altered peptide ligands and the amount of Ag dose involves the
modification of soluble factors in bulk cultures that are the driving
force that polarize the population to either a Th1 or Th2
phenotype.
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