title: Affinity and dose of TCR engagement yield proportional enhancer and gene activity in CD4+ T cells.
abstract: Affinity and dose of T cell receptor (TCR) interaction with antigens govern the magnitude of CD4+ T cell responses, but questions remain regarding the quantitative translation of TCR engagement into downstream signals. We find that while the response of mouse CD4+ T cells to antigenic stimulation is bimodal, activated cells exhibit analog responses proportional to signal strength. Gene expression output reflects TCR signal strength, providing a signature of T cell activation. Expression changes rely on a pre-established enhancer landscape and quantitative acetylation at AP-1 binding sites. Finally, we show that graded expression of activation genes depends on ERK pathway activation, suggesting that an ERK-AP-1 axis plays an important role in translating TCR signal strength into proportional activation of enhancers and genes essential for T cell function.
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, United States.|Bioinformatics and Systems Biology Program, University of California, San Diego, United States.
authors.forename: Karmel A
authors.initials: KA
authors.lastname: Allison
authors.affiliation: Department of Pediatrics, University of California, San Diego, United States.|Rady Children's Hospital, San Diego, United States.
authors.forename: Eniko
authors.initials: E
authors.lastname: Sajti
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, United States.
authors.forename: Jana G
authors.initials: JG
authors.lastname: Collier
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, United States.
authors.forename: David
authors.initials: D
authors.lastname: Gosselin
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, United States.
authors.forename: Ty Dale
authors.initials: TD
authors.lastname: Troutman
authors.affiliation: Molecular Biology Section, Division of Biological Science, University of California, San Diego, United States.|Translational Tumor Immunology Program, Wistar Institute Cancer Center, Philadelphia, United States.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Stone
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, United States.|Molecular Biology Section, Division of Biological Science, University of California, San Diego, United States.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hedrick
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, United States.|Department of Medicine, University of California, San Diego, United States.
authors.forename: Christopher K
authors.identifier: 0000-0003-4344-3592
authors.initials: CK
authors.lastname: Glass
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D015870:Gene Expression; D008213:Lymphocyte Activation; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000941:Antigens; D011948:Receptors, Antigen, T-Cell
keywords: computational biology; enhancers; immunology; mouse; protein kinase; systems biology; transcription factors