T Cell Receptor Internalization from the Immunological Synapse Is Mediated by TC21 and RhoG GTPase-Dependent Phagocytosis
Author(s)Cemerski, Saso; Delgado, Pilar; Turner, Martin; Heuser, John; Irvine, Darrell J.; Huang, Bonnie; Shaw, Andrey; Martinez-Martin, Nuria; Fernandez-Arenas, Elena; Alarcon, Balbino; Bustelo, Xose R.; ... Show more Show less
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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.
DepartmentMassachusetts Institute of Technology. Department of Biological Engineering
Martinez-Martin, Nuria, Elena Fernandez-Arenas, Saso Cemerski, Pilar Delgado, Martin Turner, John Heuser, Darrell J. Irvine, et al. “T Cell Receptor Internalization from the Immunological Synapse Is Mediated by TC21 and RhoG GTPase-Dependent Phagocytosis.” Immunity 35, no. 2 (August 2011): 208–222. © 2011 Elsevier Inc.
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