T Cell Receptor Internalization from the Immunological Synapse Is Mediated by TC21 and RhoG GTPase-Dependent Phagocytosis

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 thi...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2011-08, Vol.35 (2), p.208-222
Main Authors: Martínez-Martín, Nuria, Fernández-Arenas, Elena, Cemerski, Saso, Delgado, Pilar, Turner, Martin, Heuser, John, Irvine, Darrell J., Huang, Bonnie, Bustelo, Xosé R., Shaw, Andrey, Alarcón, Balbino
Format: Article
Language:English
Subjects:
Animals
Antigen Presentation
Antigens
Antigens - metabolism
Cell Communication
Confidence intervals
Correlation analysis
Histocompatibility Antigens Class II
Humans
Immunological Synapses - metabolism
Immunological Synapses - pathology
Jurkat Cells
Kinases
Membrane Proteins - immunology
Membrane Proteins - metabolism
Mice
Mice, Knockout
Mice, Transgenic
Monomeric GTP-Binding Proteins - immunology
Monomeric GTP-Binding Proteins - metabolism
Motion pictures
Peptide Fragments - immunology
Phagocytosis - immunology
Protein Transport
Proteins
Receptors, Antigen, T-Cell - genetics
Receptors, Antigen, T-Cell - immunology
Receptors, Antigen, T-Cell - metabolism
rho GTP-Binding Proteins - immunology
rho GTP-Binding Proteins - metabolism
Signal Transduction - immunology
Software
T cell receptors
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Summary: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. [Display omitted] ► TCR internalization from the immunological synapse is mediated by TC21 and RhoG ► T cells can phagocytose large particles by a TCR-triggered mechanism ► The GTPases TC21 and RhoG are required for TCR-triggered phagocytosis or trogocytosis ► TCR internalization by the TC21/RhoG-dependent mechanism is a phagocytic process
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2011.06.003