title: T cell receptor internalization from the immunological synapse is mediated by TC21 and RhoG GTPase-dependent phagocytosis.
abstract: The immunological synapse (IS) serves a dual role for sustained T cell receptor (TCR) signaling and for TCR downregulation. TC21 (Rras2) is a RRas subfamily GTPase that constitutively associates with the TCR and is implicated in tonic TCR signaling by activating phosphatidylinositol 3-kinase. In this study, we demonstrate that TC21 both cotranslocates with the TCR to the IS and is necessary for TCR internalization from the IS through a mechanism dependent on RhoG, a small GTPase previously associated with phagocytosis. Indeed, we found that the TCR triggers T cells to phagocytose 1-6 μm beads through a TC21- and RhoG-dependent pathway. We further show that TC21 and RhoG are necessary for the TCR-promoted uptake of major histocompatibility complex (MHC) from antigen-presenting cells. Therefore, TC21 and RhoG dependence underlie the existence of a common phagocytic mechanism that drives TCR internalization from the IS together with its peptide-MHC ligand.
authors.affiliation: Centro de Biologia Molecular Severo Ochoa, CSIC-UAM, 28049 Madrid, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Martínez-Martín
authors.forename: Elena
authors.initials: E
authors.lastname: Fernández-Arenas
authors.forename: Saso
authors.initials: S
authors.lastname: Cemerski
authors.forename: Pilar
authors.initials: P
authors.lastname: Delgado
authors.forename: Martin
authors.initials: M
authors.lastname: Turner
authors.forename: John
authors.initials: J
authors.lastname: Heuser
authors.forename: Darrell J
authors.initials: DJ
authors.lastname: Irvine
authors.forename: Bonnie
authors.initials: B
authors.lastname: Huang
authors.forename: Xosé R
authors.initials: XR
authors.lastname: Bustelo
authors.forename: Andrey
authors.initials: A
authors.lastname: Shaw
authors.forename: Balbino
authors.initials: B
authors.lastname: Alarcón
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000378:metabolism; D002450:Cell Communication; D000949:Histocompatibility Antigens Class II; D006801:Humans; D054992:Immunological Synapses / Q000378:metabolism* / Q000473:pathology; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020559:Monomeric GTP-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D021381:Protein Transport; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D020741:rho GTP-Binding Proteins / Q000276:immunology / Q000378:metabolism*
chemical_list: D000941:Antigens; D000949:Histocompatibility Antigens Class II; D008565:Membrane Proteins; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C075397:RHOG protein, human; C490200:Rras2 protein, mouse; D020559:Monomeric GTP-Binding Proteins; D020741:rho GTP-Binding Proteins