Loss of E protein transcription factors E2A and HEB delays memory-precursor formation during the CD8+T-cell immune response

The transcription factors E2A and HEB (members of the E protein family) have been shown to play essential roles in lymphocyte development, while their negative regulators, the Id proteins, have been implicated in both lymphocyte development and in the CD8+ T-cell immune response. Here, we show that E proteins also influence CD8+ T cells responding to infection. E protein expression was upregulated by CD8+ T cells during the early stages of infection and increased E protein DNA-binding activity could be detected upon TCR stimulation. Deficiency in the E proteins, E2A and HEB, led to increased frequency of terminally differentiated effector KLRG1hi CD8+ T cells in mice during infection, and decreased generation of longer-lived memory-precursor cells during the immune response. These data suggest a model whereby E protein transcription factor activity favors rapid memory-precursor T-cell formation while their negative regulators, Id2 and Id3, are both required for robust effector CD8+ T-cell response during infection.