title: Early Signaling in Primary T Cells Activated by Antigen Presenting Cells Is Associated with a Deep and Transient Lamellal Actin Network.
abstract: Cellular signaling transduction critically depends on molecular interactions that are in turn governed by dynamic subcellular distributions of the signaling system components. Comprehensive insight into signal transduction requires an understanding of such distributions and cellular structures driving them. To investigate the activation of primary murine T cells by antigen presenting cells (APC) we have imaged more than 60 signaling intermediates during T cell stimulation with microscopy across resolution limits. A substantial number of signaling intermediates associated with a transient, wide, and actin-associated lamellum extending from an interdigitated T cell:APC interface several micrometers into the T cell, as characterized in detail here. By mapping the more than 60 signaling intermediates onto the spatiotemporal features of cell biological structures, the lamellum and other ones previously described, we also define distinct spatial and temporal characteristics of T cell signal initiation, amplification, and core signaling in the activation of primary T cells by APCs. These characteristics differ substantially from ones seen when T cells are activated using common reductionist approaches.
authors.affiliation: Department of Immunology, UT Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Kole T
authors.initials: KT
authors.lastname: Roybal
authors.affiliation: Children's Hospital of Philadelphia Abramson Research Center, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Mace
authors.affiliation: School of Biochemistry, University of Bristol, Bristol, United Kingdom.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Mantell
authors.affiliation: School of Biochemistry, University of Bristol, Bristol, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Verkade
authors.affiliation: Children's Hospital of Philadelphia Abramson Research Center, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Orange
authors.affiliation: Department of Immunology, UT Southwestern Medical Center, Dallas, Texas, United States of America; Department of Cell Biology, UT Southwestern Medical Center, Dallas, Texas, United States of America; School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wülfing
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
chemical_list: D000199:Actins; D011948:Receptors, Antigen, T-Cell