title: Loss of E protein transcription factors E2A and HEB delays memory-precursor formation during the CD8+ T-cell immune response.
abstract: 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 KLRG1(hi)  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.
authors.affiliation: Division of Biology, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Louise M
authors.initials: LM
authors.lastname: D'Cruz
authors.forename: Kristin Camfield
authors.initials: KC
authors.lastname: Lind
authors.forename: Bei Bei
authors.initials: BB
authors.lastname: Wu
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Fujimoto
authors.forename: Ananda W
authors.initials: AW
authors.lastname: Goldrath
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D007156:Immunologic Memory; D051797:Inhibitor of Differentiation Protein 2 / Q000378:metabolism*; D051796:Inhibitor of Differentiation Proteins / Q000378:metabolism*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011971:Receptors, Immunologic / Q000096:biosynthesis
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D051797:Inhibitor of Differentiation Protein 2; D051796:Inhibitor of Differentiation Proteins; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; C497452:Idb2 protein, mouse; C451496:Klrg1 protein, mouse; C489532:Tcf12 protein, mouse; C075668:Tcf3 protein, mouse; C067679:Idb3 protein, mouse