The immunological synapse and the actin cytoskeleton: molecular hardware for T cell signaling

The actin cytoskeleton seems to play two critical roles in the activation of T cells. One of these roles is T cell shape development and movement, including formation of the immunological synapse. The other is the formation of a scaffold for signaling components. This review focuses on the recent convergence of cell biology and immunology studies to explain the role of the actin cytoskeleton in creating the molecular basis for immunological synapse formation and T cell signaling.

[1]  E. Elson,et al.  Preferential attachment of membrane glycoproteins to the cytoskeleton at the leading edge of lamella , 1991, The Journal of cell biology.

[2]  S. Narumiya,et al.  Inhibition of PMA-induced, LFA-1-dependent lymphocyte aggregation by ADP ribosylation of the small molecular weight GTP binding protein, rho , 1993, The Journal of cell biology.

[3]  R. Cherry,et al.  Detection of Dimers of Dimers of Human Leukocyte Antigen (HLA)–DR on the Surface of Living Cells by Single-Particle Fluorescence Imaging , 1998, The Journal of cell biology.

[4]  Michael Loran Dustin,et al.  Adhesive Bond Dynamics in Contacts between T Lymphocytes and Glass-supported Planar Bilayers Reconstituted with the Immunoglobulin-related Adhesion Molecule CD58* , 1997, The Journal of Biological Chemistry.

[5]  Rangarajan Sampath,et al.  Cytoskeletal Interactions with the Leukocyte Integrin β2 Cytoplasmic Tail , 1998, The Journal of Biological Chemistry.

[6]  Toshio Yanagida,et al.  Direct observation of single kinesin molecules moving along microtubules , 1996, Nature.

[7]  A. Trautmann,et al.  CD8 expression allows T cell signaling by monomeric peptide-MHC complexes. , 1998, Immunity.

[8]  A. Lanzavecchia,et al.  Sustained signaling leading to T cell activation results from prolonged T cell receptor occupancy. Role of T cell actin cytoskeleton , 1995, The Journal of experimental medicine.

[9]  A. Lanzavecchia,et al.  Serial triggering of many T-cell receptors by a few peptide–MHC complexes , 1995, Nature.

[10]  R. Klausner,et al.  Association of the fyn protein-tyrosine kinase with the T-cell antigen receptor. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[11]  R. Germain,et al.  The duration of antigen receptor signalling determines CD4+ versus CD8+ T-cell lineage fate , 2000, Nature.

[12]  E. Unanue,et al.  LIGAND-INDUCED MOVEMENT OF LYMPHOCYTE SURFACE MACROMOLECULES , 1974, The Journal of experimental medicine.

[13]  F. Alt,et al.  Defects in actin-cap formation in Vav-deficient mice implicate an actin requirement for lymphocyte signal transduction , 1998, Current Biology.

[14]  D. Lauffenburger,et al.  Cell Migration: A Physically Integrated Molecular Process , 1996, Cell.

[15]  E. Schaeffer,et al.  PKC-θ is required for TCR-induced NF-κB activation in mature but not immature T lymphocytes , 2000, Nature.

[16]  Partho Ghosh,et al.  Structure of the complex between human T-cell receptor, viral peptide and HLA-A2 , 1996, Nature.

[17]  Giulio Superti-Furga,et al.  Actin-based motility of vaccinia virus mimics receptor tyrosine kinase signalling , 1999, Nature.

[18]  Colin R. F. Monks,et al.  Three-dimensional segregation of supramolecular activation clusters in T cells , 1998, Nature.

[19]  F. Sánchez‐Madrid,et al.  Leukocyte polarization in cell migration and immune interactions , 1999, The EMBO journal.

[20]  N. Hogg,et al.  T cell adhesion to intercellular adhesion molecule-1 (ICAM-1) is controlled by cell spreading and the activation of integrin LFA-1. , 1996, Journal of immunology.

[21]  N. Green,et al.  Electron microscopy and structural model of human fibronectin receptor. , 1988, The EMBO journal.

[22]  A Ciechanover,et al.  Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1. , 1999, Molecular cell.

[23]  M. Cahalan,et al.  Mapping the sensitivity of T cells with an optical trap: polarity and minimal number of receptors for Ca(2+) signaling. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[24]  P. Negulescu,et al.  Polarity of T cell shape, motility, and sensitivity to antigen. , 1996, Immunity.

[25]  K. Tedford,et al.  Vav is a regulator of cytoskeletal reorganization mediated by the T-cell receptor , 1998, Current Biology.

[26]  R. Hynes,et al.  The Talin Head Domain Binds to Integrin β Subunit Cytoplasmic Tails and Regulates Integrin Activation* , 1999, The Journal of Biological Chemistry.

[27]  E. Butcher,et al.  Role of Rho in Chemoattractant-Activated Leukocyte Adhesion Through Integrins , 1996, Science.

[28]  A. Khoruts,et al.  In Vivo Detection of Dendritic Cell Antigen Presentation to CD4+ T Cells , 1997, The Journal of experimental medicine.

[29]  Z. Y. Liu,et al.  Activation of mechanical responses in leukocytes. , 1990, Biorheology.

[30]  Michael K. Rosen,et al.  Autoinhibition and activation mechanisms of the Wiskott–Aldrich syndrome protein , 2000, Nature.

[31]  B. Mayer,et al.  Regulation of PAK activation and the T cell cytoskeleton by the linker protein SLP-76. , 1998, Immunity.

[32]  J. Wehland,et al.  Fyn-Binding Protein (Fyb)/Slp-76–Associated Protein (Slap), Ena/Vasodilator-Stimulated Phosphoprotein (Vasp) Proteins and the Arp2/3 Complex Link T Cell Receptor (Tcr) Signaling to the Actin Cytoskeleton , 2000, The Journal of cell biology.

[33]  T. Harder,et al.  Clusters of glycolipid and glycosylphosphatidylinositol‐anchored proteins in lymphoid cells : accumulation of actin regulated by local tyrosine phosphorylation , 1999, European journal of immunology.

[34]  T. Mitchison,et al.  Interaction of human Arp2/3 complex and the Listeria monocytogenes ActA protein in actin filament nucleation. , 1998, Science.

[35]  L. Langeberg,et al.  Gravin, an autoantigen recognized by serum from myasthenia gravis patients, is a kinase scaffold protein , 1997, Current Biology.

[36]  C. Nobes,et al.  Rho, Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia , 1995, Cell.

[37]  Michael Loran Dustin,et al.  Making the T cell receptor go the distance: a topological view of T cell activation. , 1997, Immunity.

[38]  M. Davis,et al.  Visualizing the dynamics of T cell activation: intracellular adhesion molecule 1 migrates rapidly to the T cell/B cell interface and acts to sustain calcium levels. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[39]  C. Janeway,et al.  Physical association of CD4 with the T cell receptor. , 1992, Journal of immunology.

[40]  T. Hunter,et al.  The tyrosine kinase negative regulator c-Cbl as a RING-type, E2-dependent ubiquitin-protein ligase. , 1999, Science.

[41]  L. Langeberg,et al.  Coordination of Three Signaling Enzymes by AKAP79, a Mammalian Scaffold Protein , 1996, Science.

[42]  T. Finkel,et al.  ADP-ribosylation of rho by C3 ribosyltransferase inhibits IL-2 production and sustained calcium influx in activated T cells. , 1999, Journal of immunology.

[43]  H. Eisen,et al.  Evidence that a single peptide-MHC complex on a target cell can elicit a cytolytic T cell response. , 1996, Immunity.

[44]  T. Svitkina,et al.  Actin machinery: pushing the envelope. , 2000, Current opinion in cell biology.

[45]  Robyn L. Stanfield,et al.  An αβ T Cell Receptor Structure at 2.5 Å and Its Orientation in the TCR-MHC Complex , 1996, Science.

[46]  E. Unanue,et al.  TCR-mediated adhesion of T cell hybridomas to planar bilayers containing purified MHC class II/peptide complexes and receptor shedding during detachment. , 1996, Journal of immunology.

[47]  P. Más,et al.  A novel functional interaction between Vav and PKCtheta is required for TCR-induced T cell activation. , 2000, Immunity.

[48]  Michael Loran Dustin,et al.  Cytoskeletal polarization and redistribution of cell-surface molecules during T cell antigen recognition. , 2000, Seminars in immunology.

[49]  T. Pollard,et al.  Direct observation of dendritic actin filament networks nucleated by Arp2/3 complex and WASP/Scar proteins , 2000, Nature.

[50]  Gary G. Borisy,et al.  Self-polarization and directional motility of cytoplasm , 1999, Current Biology.

[51]  K. Schuebel,et al.  Phosphotyrosine-dependent activation of Rac-1 GDP/GTP exchange by the vav proto-oncogene product , 1997, Nature.

[52]  Michael Loran Dustin,et al.  Visualization of CD2 interaction with LFA-3 and determination of the two-dimensional dissociation constant for adhesion receptors in a contact area , 1996, The Journal of cell biology.

[53]  T D Pollard,et al.  The interaction of Arp2/3 complex with actin: nucleation, high affinity pointed end capping, and formation of branching networks of filaments. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[54]  S. Simon,et al.  GlyCAM-1, a physiologic ligand for L-selectin, activates beta 2 integrins on naive peripheral lymphocytes , 1996, The Journal of experimental medicine.

[55]  D. Plas,et al.  Direct Regulation of ZAP-70 by SHP-1 in T Cell Antigen Receptor Signaling , 1996, Science.

[56]  Gary G. Borisy,et al.  Analysis of the Actin–Myosin II System in Fish Epidermal Keratocytes: Mechanism of Cell Body Translocation , 1997, The Journal of cell biology.

[57]  Alan Aderem,et al.  Dynamic Interactions of Macrophages with T Cells during Antigen Presentation , 1999, The Journal of experimental medicine.

[58]  Daniel Choquet,et al.  Ligand binding regulates the directed movement of β1 integrins on fibroblasts , 1996, Nature.

[59]  S. Davis,et al.  The structure and ligand interactions of CD2: implications for T-cell function. , 1996, Immunology today.

[60]  A. Lanzavecchia,et al.  The duration of antigenic stimulation determines the fate of naive and effector T cells. , 1998, Immunity.

[61]  A. Lanzavecchia,et al.  T lymphocyte costimulation mediated by reorganization of membrane microdomains. , 1999, Science.

[62]  E. Martz,et al.  LFA-1 and other accessory molecules functioning in adhesions of T and B lymphocytes. , 1987, Human immunology.

[63]  L. Samelson,et al.  LAT The ZAP-70 Tyrosine Kinase Substrate that Links T Cell Receptor to Cellular Activation , 1998, Cell.

[64]  Gerhard Wagner,et al.  Structure of a Heterophilic Adhesion Complex between the Human CD2 and CD58 (LFA-3) Counterreceptors , 1999, Cell.

[65]  E. Unanue,et al.  Cutting edge: negative selection of immature thymocytes by a few peptide-MHC complexes: differential sensitivity of immature and mature T cells. , 1999, Journal of immunology.

[66]  David H. Williams,et al.  Phosphorylation of SLP-76 by the ZAP-70 Protein-tyrosine Kinase Is Required for T-cell Receptor Function* , 1996, The Journal of Biological Chemistry.

[67]  Takashi Saito,et al.  Dependence of T Cell Antigen Recognition on the Dimensions of an Accessory Receptor–Ligand Complex , 1999, The Journal of experimental medicine.

[68]  A. Bresnick Molecular mechanisms of nonmuscle myosin-II regulation. , 1999, Current opinion in cell biology.

[69]  J W Sedat,et al.  Polarization of chemoattractant receptor signaling during neutrophil chemotaxis. , 2000, Science.

[70]  Timothy A. Springer,et al.  Adhesion receptors of the immune system , 1990, Nature.

[71]  C. Figdor,et al.  Dual role of the actin cytoskeleton in regulating cell adhesion mediated by the integrin lymphocyte function-associated molecule-1. , 1997, Molecular biology of the cell.

[72]  P. Stein,et al.  pp59 fyn mutant mice display differential signaling in thymocytes and peripheral T cells , 1992, Cell.

[73]  T. Svitkina,et al.  Network contraction model for cell translocation and retrograde flow. , 1999, Biochemical Society symposium.

[74]  J. Cooper,et al.  Control of actin assembly and disassembly at filament ends. , 2000, Current opinion in cell biology.

[75]  F. Sánchez‐Madrid,et al.  CD43 interacts with moesin and ezrin and regulates its redistribution to the uropods of T lymphocytes at the cell-cell contacts. , 1998, Blood.

[76]  Michael Loran Dustin,et al.  Congenital nephrotic syndrome in mice lacking CD2-associated protein. , 1999, Science.

[77]  P. Allen,et al.  Fidelity of T cell activation through multistep T cell receptor zeta phosphorylation. , 1998, Science.

[78]  W. Paul,et al.  Lymphocyte responses and cytokines , 1994, Cell.

[79]  T. Mustelin,et al.  Regulation of the p70zap tyrosine protein kinase in T cells by the CD45 phosphotyrosine phosphatase , 1995, European journal of immunology.

[80]  E. Unanue,et al.  Two distinct mechanisms for redistribution of lymphocyte surface macromolecules. I. Relationship to cytoplasmic myosin , 1978, The Journal of cell biology.

[81]  M. Davis,et al.  A receptor/cytoskeletal movement triggered by costimulation during T cell activation. , 1998, Science.

[82]  S. Snapper,et al.  The Wiskott-Aldrich syndrome protein (WASP): roles in signaling and cytoskeletal organization. , 1999, Annual review of immunology.

[83]  A. Weiss,et al.  The role of protein tyrosine kinases and protein tyrosine phosphatases in T cell antigen receptor signal transduction. , 1994, Annual review of immunology.

[84]  Patricia L. Widder,et al.  A Novel Adaptor Protein Orchestrates Receptor Patterning and Cytoskeletal Polarity in T-Cell Contacts , 1998, Cell.

[85]  C. Figdor,et al.  Identification of DC-SIGN, a Novel Dendritic Cell–Specific ICAM-3 Receptor that Supports Primary Immune Responses , 2000, Cell.

[86]  J. Sprent,et al.  The peptide ligands mediating positive selection in the thymus control T cell survival and homeostatic proliferation in the periphery. , 1999, Immunity.

[87]  T. Springer,et al.  Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. , 1995, Annual review of physiology.

[88]  T. Chang,et al.  Crawling movements of lymphocytes on and beneath fibroblasts in culture. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[89]  T. Springer,et al.  Effect of lengthening lymphocyte function-associated antigen 3 on adhesion to CD2. , 1992, Molecular biology of the cell.

[90]  D. Shotton,et al.  The dimensions of the T lymphocyte glycoprotein leukosialin and identification of linear protein epitopes that can be modified by glycosylation. , 1991, The EMBO journal.

[91]  C. Monks,et al.  Selective modulation of protein kinase C-Θ during T-cell activation , 1997, Nature.

[92]  Philip R. Cohen,et al.  Wiskott-Aldrich syndrome protein-deficient mice reveal a role for WASP in T but not B cell activation. , 1998, Immunity.

[93]  Antonio Lanzavecchia,et al.  T Cell Activation Determined by T Cell Receptor Number and Tunable Thresholds , 1996, Science.

[94]  D A Peterson,et al.  Antigen receptor engagement delivers a stop signal to migrating T lymphocytes. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[95]  C. Monks,et al.  Selective modulation of protein kinase C-theta during T-cell activation. , 1997, Nature.

[96]  D. Portnoy,et al.  Actin filaments and the growth, movement, and spread of the intracellular bacterial parasite, Listeria monocytogenes , 1989, The Journal of cell biology.

[97]  J M Miller,et al.  Adhesion-activating phorbol ester increases the mobility of leukocyte integrin LFA-1 in cultured lymphocytes. , 1996, The Journal of clinical investigation.

[98]  S. Bromley,et al.  The immunological synapse: a molecular machine controlling T cell activation. , 1999, Science.

[99]  E. Ingulli,et al.  Visualization of specific B and T lymphocyte interactions in the lymph node. , 1998, Science.

[100]  C. Mackay,et al.  Biology of chemokine and classical chemoattractant receptors: differential requirements for adhesion-triggering versus chemotactic responses in lymphoid cells , 1996, The Journal of cell biology.

[101]  J. Hartwig,et al.  WIP, a protein associated with wiskott-aldrich syndrome protein, induces actin polymerization and redistribution in lymphoid cells. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[102]  A. Lanzavecchia Understanding the Mechanisms of Sustained Signaling and T Cell Activation , 1997, The Journal of experimental medicine.

[103]  A. Weiss,et al.  Cytoskeletal Polarization of T Cells Is Regulated by an Immunoreceptor Tyrosine-based Activation Motif–dependent Mechanism , 1998, The Journal of cell biology.

[104]  E. Butcher,et al.  A central role for microvillous receptor presentation in leukocyte adhesion under flow , 1995, Cell.

[105]  H. Nishina,et al.  Negative regulation of lymphocyte activation and autoimmunity by the molecular adaptor Cbl-b , 2000, Nature.

[106]  C. Rudd,et al.  Regulation of Vav-SLP-76 binding by ZAP-70 and its relevance to TCR zeta/CD3 induction of interleukin-2. , 1997, Immunity.

[107]  Michael Loran Dustin,et al.  The arrangement of the immunoglobulin-like domains of ICAM-1 and the binding sites for LFA-1 and rhinovirus , 1990, Cell.

[108]  Marie-France Carlier,et al.  Reconstitution of actin-based motility of Listeria and Shigella using pure proteins , 1999, Nature.

[109]  P. Wilkinson The locomotor capacity of human lymphocytes and its enhancement by cell growth. , 1986, Immunology.

[110]  R. Xavier,et al.  Membrane compartmentation is required for efficient T cell activation. , 1998, Immunity.

[111]  D. C. Edwards,et al.  Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics , 1999, Nature Cell Biology.

[112]  M. Jackson,et al.  TCR-Mediated internalization of peptide-MHC complexes acquired by T cells. , 1999, Science.

[113]  N. Hogg,et al.  LFA-1–mediated Adhesion Is Regulated by Cytoskeletal Restraint and by a Ca2+-dependent Protease, Calpain , 1998, The Journal of cell biology.

[114]  K. Robbins,et al.  Cloning and characterization of cbl-b: a SH3 binding protein with homology to the c-cbl proto-oncogene. , 1995, Oncogene.

[115]  J. Miller,et al.  TCR, LFA-1, and CD28 play unique and complementary roles in signaling T cell cytoskeletal reorganization. , 1999, Journal of immunology.

[116]  Elaine Fuchs,et al.  Directed Actin Polymerization Is the Driving Force for Epithelial Cell–Cell Adhesion , 2000, Cell.

[117]  Fanny Marhuenda,et al.  CONTACTS , 1967 .

[118]  S J Singer,et al.  Transmembrane interactions and the mechanism of capping of surface receptors by their specific ligands. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[119]  A. Trautmann,et al.  Imaging antigen recognition by naive CD4+ T cells: compulsory cytoskeletal alterations for the triggering of an intracellular calcium response , 1998, European journal of immunology.