The polarization of helper T cells is thought to be shaped mainly by the cytokine milieu. In Immunity, Germain and colleagues use intravital imaging to understand the influence of T cell antigen receptor (TCR) signaling strength and interactions with antigen-presenting dendritic cells (DCs) on the polarization of helper T cells. Adjuvants known to drive T helper type 1 (TH1) responses elicit higher expression of the costimulatory molecule CD80 on DCs and longer DC–T cell interaction times. However, strong peptide stimulation via the TCR also selectively drives TH1 polarization and, furthermore, this trumps the influence of the adjuvant. Thus, strong TCR signaling results in TH1 cells even with an otherwise 'TH2-biasing' adjuvant. TCR signaling of strong intensity upregulates expression of the β2 chain of the receptor for interleukin 12 (IL-12), which makes T cells receptive to IL-12 and TH1 biasing. The integration of TCR signals and cytokine signals therefore proceeds in a hierarchical manner.

Immunity 41, 63–74 (2014)