Many factors influence polarization of CD4 T cells to Th1 or Th2, including those collectively termed ‘strength of stimulation', such as peptide dose and duration of T-cell receptor (TCR) engagement. When other factors dictate the need for a Th1 or Th2 response, there might be selection from the TCR pool, selecting for those with optimal affinity for the desired cytokine profile. In a Th2 environment, this would entail selection from the bulk population of lower affinity receptors, causing differential signaling and favoring transcription of Th2 cytokines. Reliance on experiments using a single, transgenic TCR polarized into either subset might have obscured the fact that, under physiological conditions, there is selection for differential TCRs on the basis of affinity.