Peptide affinity as a major determinant for differentiation into Th1/Th2 phenotypes

Two opposing viewpoints exist regarding how antigen dose and affinity modulate Th1/Th2 differentiation: high level or low level stimulation may favor Th2 responses. Using peptides varying in affinity for the TCR, we present novel data that validates both arguments, and show that the period of differentiation is the determining factor. Over short term, the level of stimulation needed for Th2 cytokines was greater than for Th1 cytokines. Over long term, high dose/high affinity peptides led to IFN-gamma-secreting cells, while IL-5-secreting cells predominated with lower levels of initial signaling. These results help resolve the controversy over the effects of dose and affinity, and suggest a unifying model of Th1/Th2 differentiation based on strength of signaling and time of differentiation.