Affinity and dose of TCR engagement yield proportional enhancer and gene activity in CD4+ T cells
Karmel A Allison,
Eniko Sajti,
Jana G Collier,
David Gosselin,
Ty Dale Troutman,
Erica L Stone,
Stephen M Hedrick,
Christopher K Glass
Affiliations
Karmel A Allison
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
Eniko Sajti
Department of Pediatrics, University of California, San Diego, United States; Rady Children's Hospital, San Diego, United States
Jana G Collier
Department of Cellular and Molecular Medicine, University of California, San Diego, United States
David Gosselin
Department of Cellular and Molecular Medicine, University of California, San Diego, United States
Ty Dale Troutman
Department of Cellular and Molecular Medicine, University of California, San Diego, United States
Erica L Stone
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
Stephen M Hedrick
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
Department of Cellular and Molecular Medicine, University of California, San Diego, United States; Department of Medicine, University of California, San Diego, United States
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.
