title: A large T cell invagination with CD2 enrichment resets receptor engagement in the immunological synapse.
abstract: T cell activation is driven by the TCR and complemented by costimulation. We have studied the dynamics of ligand-engagement of the costimulatory receptor CD2 in T cell/APC couples. Thousands of ligand-engaged CD2 molecules were included in a large T cell invagination at the center of the cellular interface within 1 min of cell couple formation. The structure and regulation of this invagination shared numerous features with phagocytosis and macropinocytosis. Three observations further characterize the invagination and the inclusion of CD2: 1) numerous ligand-engaged receptors were enriched in and internalized through the T cell invagination, none as prominently as CD2; 2) dissolution of the T cell invagination and CD2 engagement were required for effective proximal T cell signaling; and 3) the T cell invagination was uniquely sensitive to the affinity of the TCR for peptide-MHC. Based on this characterization, we speculate that the T cell invagination, aided by CD2 enrichment, internalizes parts of the TCR signaling machinery to reset T cell signaling upon agonist-mediated, stable APC contact.
authors.affiliation: Center for Immunology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Kentner
authors.initials: K
authors.lastname: Singleton
authors.forename: Nadia
authors.initials: N
authors.lastname: Parvaze
authors.forename: Kavyya R
authors.initials: KR
authors.lastname: Dama
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Chen
authors.forename: Paula
authors.initials: P
authors.lastname: Jennings
authors.forename: Bozidar
authors.initials: B
authors.lastname: Purtic
authors.forename: Michael D
authors.initials: MD
authors.lastname: Sjaastad
authors.forename: Christopher
authors.initials: C
authors.lastname: Gilpin
authors.forename: Mark M
authors.initials: MM
authors.lastname: Davis
authors.forename: Christoph
authors.initials: C
authors.lastname: Wülfing
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000648:ultrastructure*; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D018801:CD2 Antigens / Q000276:immunology / Q000378:metabolism*; D000071178:CD48 Antigen; D004705:Endocytosis / Q000276:immunology; D007091:Image Processing, Computer-Assisted; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure*
chemical_list: D000199:Actins; D015703:Antigens, CD; D018801:CD2 Antigens; D000071178:CD48 Antigen; D011948:Receptors, Antigen, T-Cell