Skip to main content
SpringerLink
Log in
Book cover

Immunological Synapse pp 1–24Cite as

Insights into Function of the Immunological Synapse from Studies with Supported Planar Bilayers

  • Chapter
  • First Online:

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 340))

Abstract

Innate and adaptive immunity is dependent upon reliable cell–cell communication mediated by direct interactions of cell surface receptors with ligands integrated into the surface of apposing cells or bound directly to the surface as in complement deposition or antibody mediated recognition through Fc receptors. Supported lipid bilayers formed on glass surfaces offer a useful model system in which to explore some basic features of molecular interactions in immunological relevant contacts, which include signal integration and effector functions through immunological synapses and kinapses. We have exploited that lateral mobility of molecules in the supported planar bilayers and fluorescence microscopy to develop a system for measurement of two-dimensional affinities and kinetic rates in the contact area, which is of immunological interest. Affinity measurements are based on a modified Scatchard analysis. Measurements of kinetic rates are based on fluorescence photo bleaching after recovery at the level of the entire contact area. This has been coupled to a reaction–diffusion equation that allows calculation of on- and off-rates. We have found that mixtures of ligands in supported planar bilayers can effectively activate T lymphocytes and simultaneously allow monitoring of the immunological synapse. Recent studies in planar bilayers have provided additional insights into organization principles of cell–cell interfaces. Perennial problems in understanding cell–cell communication are yielding quantitative measurements based on planar bilayers in areas of ligand-driven receptor clustering and the role of the actin cytoskeleton in immune cell activation. A major goal for the field is determining quantitative rules involved in signaling complex formation by innate and adaptive receptor systems.

This is a preview of subscription content, log in via an institution.

Abbreviations

BCR:

B-cell antigen receptor

LFA:

Lymphocyte function associated

PKC:

Protein kinase C

SMAC:

Supramolecular activation cluster

TCR:

T-cell antigen receptor

TIRF:

Total internal reflection fluorescence

References

  • Al-Alwan MM, Rowden G, Lee TD, West KA (2001a) Fascin is involved in the antigen presentation activity of mature dendritic cells. J Immunol 166:338–345

    CAS  PubMed  Google Scholar 

  • Al-Alwan MM, Rowden G, Lee TD, West KA (2001b) The dendritic cell cytoskeleton is critical for the formation of the immunological synapse. J Immunol 166:1452–1456

    CAS  PubMed  Google Scholar 

  • Babbitt BP, Allen PM, Matsueda G, Haber E, Unanue ER (1985) Binding of immunogenic peptides to Ia histocompatibility molecules. Nature 317:359–361

    Article  CAS  PubMed  Google Scholar 

  • Batista FD, Iber D, Neuberger MS (2001) B cells acquire antigen from target cells after synapse formation. Nature 411:489–494

    Article  CAS  PubMed  Google Scholar 

  • Beal AM, Anikeeva N, Varma R, Cameron TO, Norris PJ, Dustin ML, Sykulev Y (2008) Protein kinase C{theta} regulates stability of the peripheral adhesion ring junction and contributes to the sensitivity of target cell lysis by CTL. J Immunol 181:4815–4824

    CAS  PubMed  Google Scholar 

  • Bonte F, Juliano RL (1986) Interactions of liposomes with serum proteins. Chem Phys Lipids 40:359–372

    Article  CAS  PubMed  Google Scholar 

  • Breart B, Lemaitre F, Celli S, Bousso P (2008) Two-photon imaging of intratumoral CD8+ T cell cytotoxic activity during adoptive T cell therapy in mice. J Clin Invest 118:1390–1397

    Article  CAS  PubMed  Google Scholar 

  • Brian AA, McConnell HM (1984) Allogeneic stimulation of cytotoxic T cells by supported planar membranes. Proc Natl Acad Sci USA 81:6159–6163

    Article  CAS  PubMed  Google Scholar 

  • Bromley SK, Iaboni A, Davis SJ, Whitty A, Green JM, Shaw AS, Weiss A, Dustin ML (2001) The immunological synapse and CD28-CD80 interactions. Nat Immunol 2:1159–1166

    Article  CAS  PubMed  Google Scholar 

  • Brossard C, Feuillet V, Schmitt A, Randriamampita C, Romao M, Raposo G, Trautmann A (2005) Multifocal structure of the T cell – dendritic cell synapse. Eur J Immunol 35:1741–1753

    Article  CAS  PubMed  Google Scholar 

  • Bunnell SC, Hong DI, Kardon JR, Yamazaki T, McGlade CJ, Barr VA, Samelson LE (2002) T cell receptor ligation induces the formation of dynamically regulated signaling assemblies. J Cell Biol 158:1263–1275

    Article  CAS  PubMed  Google Scholar 

  • Campi G, Varma R, Dustin ML (2005) Actin and agonist MHC–peptide complex-dependent T cell receptor microclusters as scaffolds for signaling. J Exp Med 202:1031–1036

    Article  CAS  PubMed  Google Scholar 

  • Carman CV, Sage PT, Sciuto TE, de la Fuente MA, Geha RS, Ochs HD, Dvorak HF, Dvorak AM, Springer TA (2007) Transcellular diapedesis is initiated by invasive podosomes. Immunity 26:784–797

    Article  CAS  PubMed  Google Scholar 

  • Carrasco YR, Fleire SJ, Cameron T, Dustin ML, Batista FD (2004) LFA-1/ICAM-1 interaction lowers the threshold of B cell activation by facilitating B cell adhesion and synapse formation. Immunity 20:589–599

    Article  CAS  PubMed  Google Scholar 

  • Chan PY, Lawrence MB, Dustin ML, Ferguson LM, Golan DE, Springer TA (1991) Influence of receptor lateral mobility on adhesion strengthening between membranes containing LFA-3 and CD2. J Cell Biol 115:245–255

    Article  CAS  PubMed  Google Scholar 

  • Chang JT, Palanivel VR, Kinjyo I, Schambach F, Intlekofer AM, Banerjee A, Longworth SA, Vinup KE, Mrass P, Oliaro J, Killeen N, Orange JS, Russell SM, Weninger W, Reiner SL (2007) Asymmetric T lymphocyte division in the initiation of adaptive immune responses. Science 315:1687–1691

    Article  CAS  PubMed  Google Scholar 

  • Choi CK, Vicente-Manzanares M, Zareno J, Whitmore LA, Mogilner A, Horwitz AR (2008) Actin and alpha-actinin orchestrate the assembly and maturation of nascent adhesions in a myosin II motor-independent manner. Nat Cell Biol 10:1039–1050

    Article  CAS  PubMed  Google Scholar 

  • Choudhuri K, Wiseman D, Brown MH, Gould K, van der Merwe PA (2005) T-cell receptor triggering is critically dependent on the dimensions of its peptide-MHC ligand. Nature 436:578–582

    Article  CAS  PubMed  Google Scholar 

  • DeMond AL, Mossman KD, Starr T, Dustin ML, Groves JT (2008) T cell receptor microcluster transport through molecular mazes reveals mechanism of translocation. Biophys J 94:3286–3292

    Article  CAS  PubMed  Google Scholar 

  • Depoil D, Fleire S, Treanor BL, Weber M, Harwood NE, Marchbank KL, Tybulewicz VL, Batista FD (2008) CD19 is essential for B cell activation by promoting B cell receptor-antigen microcluster formation in response to membrane-bound ligand. Nat Immunol 9:63–72

    Article  CAS  PubMed  Google Scholar 

  • Dustin ML (1997) Adhesive bond dynamics in contacts between T lymphocytes and glass supported planar bilayers reconstituted with the immunoglobulin related adhesion molecule CD58. J Biol Chem 272:15782–15788

    Article  CAS  PubMed  Google Scholar 

  • Dustin ML (2008) Hunter to gatherer and back: immunological synapses and kinapses as variations on the theme of amoeboid locomotion. Annu Rev Cell Dev Biol 24:577–596

    Article  CAS  PubMed  Google Scholar 

  • Dustin ML, Chan AC (2000) Signaling takes shape in the immune system. Cell 103:283–294

    Article  CAS  PubMed  Google Scholar 

  • Dustin ML, Colman DR (2002) Neural and immunological synaptic relations. Science 298:785–789

    Article  CAS  PubMed  Google Scholar 

  • Dustin ML, Cooper JA (2000) The immunological synapse and the actin cytoskeleton: molecular hardware for T cell signaling. Nat Immunol 1:23–29

    Article  CAS  PubMed  Google Scholar 

  • Dustin ML, Shaw AS (1999) Costimulation: building an immunological synapse. Science 283:649–650

    Article  CAS  PubMed  Google Scholar 

  • Dustin ML, Springer TA (1988) Lymphocyte function-associated antigen-1 (LFA-1) interaction with intercellular adhesion molecule-1 (ICAM-1) is one of at least three mechanisms for lymphocyte adhesion to cultured endothelial cells. J Cell Biol 107:321–331

    Article  CAS  PubMed  Google Scholar 

  • Dustin ML, Springer TA (1989) T cell receptor cross-linking transiently stimulates adhesiveness through LFA-1. Nature 341:619–624

    Article  CAS  PubMed  Google Scholar 

  • Dustin ML, Sanders ME, Shaw S, Springer TA (1987a) Purified lymphocyte function-associated antigen 3 binds to CD2 and mediates T lymphocyte adhesion. J Exp Med 165:677–692

    Article  CAS  PubMed  Google Scholar 

  • Dustin ML, Selvaraj P, Mattaliano RJ, Springer TA (1987b) Anchoring mechanisms for LFA-3 cell adhesion glycoprotein at membrane surface. Nature 329:846–848

    Article  CAS  PubMed  Google Scholar 

  • Dustin ML, Singer KH, Tuck DT, Springer TA (1988) Adhesion of T lymphoblasts to epidermal keratinocytes is regulated by interferon gamma and is mediated by intercellular adhesion molecule 1 (ICAM-1). J Exp Med 167:1323–1340

    Article  CAS  PubMed  Google Scholar 

  • Dustin ML, Ferguson LM, Chan PY, Springer TA, Golan DE (1996a) Visualization of CD2 interaction with LFA-3 and determination of the two-dimensional dissociation constant for adhesion receptors in a contact area. J Cell Biol 132:465–474

    Article  CAS  PubMed  Google Scholar 

  • Dustin ML, Miller JM, Ranganath S, Vignali DA, Viner NJ, Nelson CA, Unanue ER (1996b) TCR-mediated adhesion of T cell hybridomas to planar bilayers containing purified MHC class II/peptide complexes and receptor shedding during detachment. J Immunol 157:2014–2021

    CAS  PubMed  Google Scholar 

  • Dustin ML, Bromley SK, Kan Z, Peterson DA, Unanue ER (1997a) Antigen receptor engagement delivers a stop signal to migrating T lymphocytes. Proc Natl Acad Sci USA 94:3909–3913

    Article  CAS  PubMed  Google Scholar 

  • Dustin ML, Golan DE, Zhu DM, Miller JM, Meier W, Davies EA, van der Merwe PA (1997b) Low affinity interaction of human or rat T cell adhesion molecule CD2 with its ligand aligns adhering membranes to achieve high physiological affinity. J Biol Chem 272:30889–30898

    Article  CAS  PubMed  Google Scholar 

  • Dustin ML, Olszowy MW, Holdorf AD, Li J, Bromley S, Desai N, Widder P, Rosenberger F, van der Merwe PA, Allen PM, Shaw AS (1998) A novel adapter protein orchestrates receptor patterning and cytoskeletal polarity in T cell contacts. Cell 94:667–677

    Article  CAS  PubMed  Google Scholar 

  • Dustin ML, Starr T, Coombs D, Majeau GR, Meier W, Hochman PS, Douglass A, Vale R, Goldstein B, Whitty A (2007a) Quantification and modeling of Tripartite CD2-, CD58FC chimera (Alefacept)-, and CD16-mediated cell adhesion. J Biol Chem 282:34748–34757

    Article  CAS  PubMed  Google Scholar 

  • Dustin ML, Starr T, Varma R, Thomas VK (2007) Supported planar bilayers for study of the immunological synapse. Curr Protoc Immunol, Chapter 18, Unit 18.13

    Google Scholar 

  • Fischer KD, Kong YY, Nishina H, Tedford K, Marengere LE, Kozieradzki I, Sasaki T, Starr M, Chan G, Gardener S, Nghiem MP, Bouchard D, Barbacid M, Bernstein A, Penninger JM (1998) Vav is a regulator of cytoskeletal reorganization mediated by the T-cell receptor. Curr Biol 8:554–562

    Article  CAS  PubMed  Google Scholar 

  • Fleire SJ, Goldman JP, Carrasco YR, Weber M, Bray D, Batista FD (2006) B cell ligand discrimination through a spreading and contraction response. Science 312:738–741

    Article  CAS  PubMed  Google Scholar 

  • Freiberg BA, Kupfer H, Maslanik W, Delli J, Kappler J, Zaller DM, Kupfer A (2002) Staging and resetting T cell activation in SMACs. Nat Immunol 3:911–917

    Article  CAS  PubMed  Google Scholar 

  • Galbraith CG, Yamada KM, Sheetz MP (2002) The relationship between force and focal complex development. J Cell Biol 159:695–705

    Article  CAS  PubMed  Google Scholar 

  • Gay D, Coeshott C, Golde W, Kappler J, Marrack P (1986) The major histocompatibility complex-restricted antigen receptor on T cells. IX. Role of accessory molecules in recognition of antigen plus isolated IA. J Immunol 136:2026–2032

    CAS  PubMed  Google Scholar 

  • Gil D, Schamel WW, Montoya M, Sanchez-Madrid F, Alarcon B (2002) Recruitment of Nck by CD3 epsilon reveals a ligand-induced conformational change essential for T cell receptor signaling and synapse formation. Cell 109:901–912

    Article  CAS  PubMed  Google Scholar 

  • Gomez TS, Kumar K, Medeiros RB, Shimizu Y, Leibson PJ, Billadeau DD (2007) Formins regulate the actin-related protein 2/3 complex-independent polarization of the centrosome to the immunological synapse. Immunity 26:177–190

    Article  CAS  PubMed  Google Scholar 

  • Grakoui A, Bromley SK, Sumen C, Davis MM, Shaw AS, Allen PM, Dustin ML (1999) The immunological synapse: a molecular machine controlling T cell activation. Science 285:221–227

    Article  CAS  PubMed  Google Scholar 

  • Gunzer M, Schafer A, Borgmann S, Grabbe S, Zanker KS, Brocker EB, Kampgen E, Friedl P (2000) Antigen presentation in extracellular matrix: interactions of T cells with dendritic cells are dynamic, short lived, and sequential. Immunity 13:323–332

    Article  CAS  PubMed  Google Scholar 

  • Hafeman DG, von Tscharner V, McConnell HM (1981) Specific antibody-dependent interactions between macrophages and lipid haptens in planar lipid monolayers. Proc Natl Acad Sci USA 78:4552–4556

    Article  CAS  PubMed  Google Scholar 

  • Hollander N, Selvaraj P, Springer TA (1988) Biosynthesis and function of LFA-3 in human mutant cells deficient in phosphatidylinositol anchored proteins. J Immunol 141:4283–4290

    CAS  PubMed  Google Scholar 

  • Ilani T, Vasiliver-Shamis G, Vardhana S, Bretscher A, Dustin ML (2009) T cell antigen receptor signaling and immunological synapse stability require myosin IIA. Nat Immunol 10:531–539

    Article  CAS  PubMed  Google Scholar 

  • Izzard CS, Lochner LR (1976) Cell-to-substrate contacts in living fibroblasts: an interference reflexion study with an evaluation of the technique. J Cell Sci 21:129–159

    CAS  PubMed  Google Scholar 

  • Jacobelli J, Chmura SA, Buxton DB, Davis MM, Krummel MF (2004) A single class II myosin modulates T cell motility and stopping, but not synapse formation. Nat Immunol 5:531–538

    Article  CAS  PubMed  Google Scholar 

  • Kaizuka Y, Douglass AD, Varma R, Dustin ML, Vale RD (2007) Mechanisms for segregating T cell receptor and adhesion molecules during immunological synapse formation in Jurkat T cells. Proc Natl Acad Sci USA 104:20296–20301

    Article  CAS  PubMed  Google Scholar 

  • Kaizuka Y, Douglass AD, Vardhana S, Dustin ML, Vale RD (2009) The coreceptor CD2 uses plasma membrane microdomains to transduce signals in T cells. J Cell Biol 185:521–534

    Article  CAS  PubMed  Google Scholar 

  • Kloboucek A, Behrisch A, Faix J, Sackmann E (1999) Adhesion-induced receptor segregation and adhesion plaque formation: a model membrane study. Biophys J 77:2311–2328

    Article  CAS  PubMed  Google Scholar 

  • Krummel MF, Sjaastad MD, Wulfing C, Davis MM (2000) Differential clustering of CD4 and CD3ζ during T cell recognition. Science 289:1349–1352

    Article  CAS  PubMed  Google Scholar 

  • Lee KH, Holdorf AD, Dustin ML, Chan AC, Allen PM, Shaw AS (2002) T cell receptor signaling precedes immunological synapse formation. Science 295:1539–1542

    Article  CAS  PubMed  Google Scholar 

  • Lee KH, Dinner AR, Tu C, Campi G, Raychaudhuri S, Varma R, Sims TN, Burack WR, Wu H, Wang J, Kanagawa O, Markiewicz M, Allen PM, Dustin ML, Chakraborty AK, Shaw AS (2003) The immunological synapse balances T cell receptor signaling and degradation. Science 302:1218–1222

    Article  CAS  PubMed  Google Scholar 

  • Liu D, Bryceson YT, Meckel T, Vasiliver-Shamis G, Dustin ML, Long EO (2009) Integrin-dependent organization and bidirectional vesicular traffic at cytotoxic immune synapses. Immunity (in press)

    Google Scholar 

  • Lomnitzer R, Rabson AR (1981) Mechanism of suppression of lymphocyte proliferation by Concanavalin A-activated mononuclear cells. Immunology 43:475–481

    CAS  PubMed  Google Scholar 

  • Lucas M, Schachterle W, Oberle K, Aichele P, Diefenbach A (2007) Dendritic cells prime natural killer cells by trans-presenting interleukin 15. Immunity 26:503–517

    Article  CAS  PubMed  Google Scholar 

  • Luo BH, Carman CV, Springer TA (2007) Structural basis of integrin regulation and signaling. Annu Rev Immunol 25:619–647

    Article  CAS  PubMed  Google Scholar 

  • Marlin SD, Springer TA (1987) Purified intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen 1 (LFA-1). Cell 51:813–819

    Article  CAS  PubMed  Google Scholar 

  • McKeithan TW (1995) Kinetic proofreading in T-cell receptor signal transduction. Proc Natl Acad Sci USA 92:5042–5046

    Article  CAS  PubMed  Google Scholar 

  • Mempel TR, Henrickson SE, Von Andrian UH (2004) T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases. Nature 427:154–159

    Article  CAS  PubMed  Google Scholar 

  • Mescher MF (1992) Surface contact requirements for activation of cytotoxic T lymphocytes. J Immunol 149:2402–2405

    CAS  PubMed  Google Scholar 

  • Metzger H (1992) Transmembrane signaling: the joy of aggregation. J Immunol 149:1477–1487

    CAS  PubMed  Google Scholar 

  • Milstein O, Tseng SY, Starr T, Llodra J, Nans A, Liu M, Wild MK, van der Merwe PA, Stokes DL, Reisner Y, Dustin ML (2008) Nanoscale increases in CD2-CD48-mediated intermembrane spacing decrease adhesion and reorganize the immunological synapse. J Biol Chem 283:34414–34422

    Article  CAS  PubMed  Google Scholar 

  • Monks CR, Freiberg BA, Kupfer H, Sciaky N, Kupfer A (1998) Three-dimensional segregation of supramolecular activation clusters in T cells. Nature 395:82–86

    Article  CAS  PubMed  Google Scholar 

  • Mossman KD, Campi G, Groves JT, Dustin ML (2005) Altered TCR signaling from geometrically repatterned immunological synapses. Science 310:1191–1193

    Article  CAS  PubMed  Google Scholar 

  • Negulescu PA, Krasieva TB, Khan A, Kerschbaum HH, Cahalan MD (1996) Polarity of T cell shape, motility, and sensitivity to antigen. Immunity 4:421–430

    Article  CAS  PubMed  Google Scholar 

  • Nguyen K, Sylvain NR, Bunnell SC (2008) T cell costimulation via the integrin VLA-4 inhibits the actin-dependent centralization of signaling microclusters containing the adaptor SLP-76. Immunity 28:810–821

    Article  CAS  PubMed  Google Scholar 

  • Nolz JC, Gomez TS, Zhu P, Li S, Medeiros RB, Shimizu Y, Burkhardt JK, Freedman BD, Billadeau DD (2006) The WAVE2 complex regulates actin cytoskeletal reorganization and CRAC-mediated calcium entry during T cell activation. Curr Biol 16:24–34

    Article  CAS  PubMed  Google Scholar 

  • Norcross MA (1984) A synaptic basis for T-lymphocyte activation. Ann Immunol (Paris) 135D:113–134

    CAS  Google Scholar 

  • Oddos S, Dunsby C, Purbhoo MA, Chauveau A, Owen DM, Neil MA, Davis DM, French PM (2008) High-speed high-resolution imaging of intercellular immune synapses using optical tweezers. Biophys J 95:L66–L68

    Article  PubMed  CAS  Google Scholar 

  • Parthasarathy R, Groves JT (2006) Coupled membrane fluctuations and protein mobility in supported intermembrane junctions. J Phys Chem B 110:8513–8516

    Article  CAS  PubMed  Google Scholar 

  • Pierres A, Benoliel AM, Bongrand P, van der Merwe PA (1996) Determination of the lifetime and force dependence of interactions of single bonds between surface-attached CD2 and CD48 adhesion molecules. Proc Natl Acad Sci USA 93:15114–15118

    Article  CAS  PubMed  Google Scholar 

  • Reich Z, Boniface JJ, Lyons DS, Borochov N, Wachtel EJ, Davis MM (1997) Ligand-specific oligomerization of T-cell receptor molecules. Nature 387:617–620

    Article  CAS  PubMed  Google Scholar 

  • Rothlein R, Dustin ML, Marlin SD, Springer TA (1986) A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1. J Immunol 137:1270–1274

    CAS  PubMed  Google Scholar 

  • Samelson LE, Patel MD, Weissman AM, Harford JB, Klausner RD (1986) Antigen activation of murine T cells induces tyrosine phosphorylation of a polypeptide associated with the T cell antigen receptor. Cell 46:1083–1090

    Article  CAS  PubMed  Google Scholar 

  • Sanchez-Madrid F, Krensky AM, Ware CF, Robbins E, Strominger JL, Burakoff SJ, Springer TA (1982) Three distinct antigens associated with human T-lymphocyte-mediated cytolysis: LFA-1, LFA-2, and LFA-3. Proc Natl Acad Sci USA 79:7489–7493

    Article  CAS  PubMed  Google Scholar 

  • Scatchard G (1949) The attractions of proteins for small molecules and ions. Ann NY Acad Sci 51:660–672

    Article  CAS  Google Scholar 

  • Schlessinger J, Webb WW, Elson EL, Metzger H (1976) Lateral motion and valence of Fc receptors on rat peritoneal mast cells. Nature 264:550–552

    Article  CAS  PubMed  Google Scholar 

  • Scholer A, Hugues S, Boissonnas A, Fetler L, Amigorena S (2008) Intercellular adhesion molecule-1-dependent stable interactions between T cells and dendritic cells determine CD8+ T cell memory. Immunity 28:258–270

    Article  CAS  PubMed  Google Scholar 

  • Shao JY, Yu Y, Dustin ML (2005) A model for CD2/CD58-mediated adhesion strengthening. Ann Biomed Eng 33:483–493

    Article  PubMed  Google Scholar 

  • Shaw AS, Dustin ML (1997) Making the T cell receptor go the distance: a topological view of T cell activation. Immunity 6:361–369

    Article  CAS  PubMed  Google Scholar 

  • Shaw S, Luce GE, Quinones R, Gress RE, Springer TA, Sanders ME (1986) Two antigen-independent adhesion pathways used by human cytotoxic T-cell clones. Nature 323:262–264

    Article  CAS  PubMed  Google Scholar 

  • Shimaoka M, Xiao T, Liu JH, Yang Y, Dong Y, Jun CD, McCormack A, Zhang R, Joachimiak A, Takagi J, Wang JH, Springer TA (2003) Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation. Cell 112:99–111

    Article  CAS  PubMed  Google Scholar 

  • Sims TN, Soos TJ, Xenias HS, Dubin-Thaler B, Hofman JM, Waite JC, Cameron TO, Thomas VK, Varma R, Wiggins CH, Sheetz MP, Littman DR, Dustin ML (2007) Opposing effects of PKCtheta and WASp on symmetry breaking and relocation of the immunological synapse. Cell 129:773–785

    Article  CAS  PubMed  Google Scholar 

  • Skokos D, Shakhar G, Varma R, Waite JC, Cameron TO, Lindquist RL, Schwickert T, Nussenzweig MC, Dustin ML (2007) Peptide-MHC potency governs dynamic interactions between T cells and dendritic cells in lymph nodes. Nat Immunol 8:835–844

    Article  CAS  PubMed  Google Scholar 

  • Smith A, Carrasco YR, Stanley P, Kieffer N, Batista FD, Hogg N (2005) A talin-dependent LFA-1 focal zone is formed by rapidly migrating T lymphocytes. J Cell Biol 170:141–151

    Article  CAS  PubMed  Google Scholar 

  • Springer TA (1990) Adhesion receptors of the immune system. Nature 346:425–434

    Article  CAS  PubMed  Google Scholar 

  • Stauffer TP, Meyer T (1997) Compartmentalized IgE receptor-mediated signal transduction in living cells. J Cell Biol 139:1447–1454

    Article  CAS  PubMed  Google Scholar 

  • Stinchcombe JC, Majorovits E, Bossi G, Fuller S, Griffiths GM (2006) Centrosome polarization delivers secretory granules to the immunological synapse. Nature 443:462–465

    Article  CAS  PubMed  Google Scholar 

  • Tolar P, Sohn HW, Pierce SK (2005) The initiation of antigen-induced B cell antigen receptor signaling viewed in living cells by fluorescence resonance energy transfer. Nat Immunol 6:1168–1176

    Article  CAS  PubMed  Google Scholar 

  • Tolar P, Hanna J, Krueger PD, Pierce SK (2009) The constant region of the membrane immunoglobulin mediates B cell-receptor clustering and signaling in response to membrane antigens. Immunity 30:44–55

    Article  CAS  PubMed  Google Scholar 

  • Tolentino TP, Wu J, Zarnitsyna VI, Fang Y, Dustin ML, Zhu C (2008) Measuring diffusion and binding kinetics by contact area FRAP. Biophys J 95:920–930

    Article  CAS  PubMed  Google Scholar 

  • Torigoe C, Song J, Barisas BG, Metzger H (2004) The influence of actin microfilaments on signaling by the receptor with high-affinity for IgE. Mol Immunol 41:817–829

    Article  CAS  PubMed  Google Scholar 

  • Tseng SY, Waite JC, Liu M, Vardhana S, Dustin ML (2008) T cell-dendritic cell immunological synapses contain TCR-dependent CD28-CD80 clusters that recruit protein kinase Ctheta. J Immunol 181:4852–4863

    CAS  PubMed  Google Scholar 

  • Van Der Merwe PA, Davis SJ (2003) Molecular interactions mediating T cell antigen recognition. Annu Rev Immunol 21:659–684

    Article  PubMed  CAS  Google Scholar 

  • van der Merwe PA, Barclay AN, Mason DW, Davies EA, Morgan BP, Tone M, Krishnam AKC, Ianelli C, Davis SJ (1994) Human cell-adhesion molecule CD2 binds CD58 (LFA-3) with a very low affinity and an extremely fast dissociation rate but does not bind CD48 or CD59. Biochemistry 33:10149–10160

    Article  PubMed  Google Scholar 

  • Varma R, Campi G, Yokosuka T, Saito T, Dustin ML (2006) T cell receptor-proximal signals are sustained in peripheral microclusters and terminated in the central supramolecular activation cluster. Immunity 25:117–127

    Article  CAS  PubMed  Google Scholar 

  • Watts TH, McConnell HM (1986) High-affinity fluorescent peptide binding to I-Ad in lipid membranes. Proc Natl Acad Sci USA 83:9660–9664

    Article  CAS  PubMed  Google Scholar 

  • Watts TH, Gaub HE, McConnell HM (1986) T-cell-mediated association of peptide antigen and major histocompatibility complex protein detected by energy transfer in an evanescent wave-field. Nature 320:179–181

    Article  CAS  PubMed  Google Scholar 

  • Weikl TR, Lipowsky R (2004) Pattern formation during T-cell adhesion. Biophys J 87:3665–3678

    Article  CAS  PubMed  Google Scholar 

  • Weis RM, Balakrishnan K, Smith BA, McConnell HM (1982) Stimulation of fluorescence in a small contact region between rat basophil leukemia cells and planar lipid membrane targets by coherent evanescent radiation. J Biol Chem 257:6440–6445

    CAS  PubMed  Google Scholar 

  • Wherry EJ, Ahmed R (2004) Memory CD8 T-cell differentiation during viral infection. J Virol 78:5535–5545

    Article  CAS  PubMed  Google Scholar 

  • Wild MK, Cambiaggi A, Brown MH, Davies EA, Ohno H, Saito T, van der Merwe PA (1999) Dependence of T cell antigen recognition on the dimensions of an accessory receptor-ligand complex. J Exp Med 190:31–41

    Article  CAS  PubMed  Google Scholar 

  • Woolf E, Grigorova I, Sagiv A, Grabovsky V, Feigelson SW, Shulman Z, Hartmann T, Sixt M, Cyster JG, Alon R (2007) Lymph node chemokines promote sustained T lymphocyte motility without triggering stable integrin adhesiveness in the absence of shear forces. Nat Immunol 8:1076–1085

    Article  CAS  PubMed  Google Scholar 

  • Wu J, Fang Y, Zarnitsyna VI, Tolentino TP, Dustin ML, Zhu C (2008) A coupled diffusion-kinetics model for analysis of contact-area FRAP experiment. Biophys J 95:910–919

    Article  CAS  PubMed  Google Scholar 

  • Wülfing C, Davis MM (1998) A Receptor/cytoskeletal movement triggered by costimulation during T cell activation. Science 282:2266–2269

    Article  PubMed  Google Scholar 

  • Xu C, Gagnon E, Call ME, Schnell JR, Schwieters CD, Carman CV, Chou JJ, Wucherpfennig KW (2008) Regulation of T cell receptor activation by dynamic membrane binding of the CD3epsilon cytoplasmic tyrosine-based motif. Cell 135:702–713

    Article  CAS  PubMed  Google Scholar 

  • Yokosuka T, Sakata-Sogawa K, Kobayashi W, Hiroshima M, Hashimoto-Tane A, Tokunaga M, Dustin ML, Saito T (2005) Newly generated T cell receptor microclusters initiate and sustain T cell activation by recruitment of Zap70 and SLP-76. Nat Immunol 6:1253–1262

    Article  CAS  PubMed  Google Scholar 

  • Yokosuka T, Kobayashi W, Sakata-Sogawa K, Takamatsu M, Hashimoto-Tane A, Dustin ML, Tokunaga M, Saito T (2008) Spatiotemporal regulation of T cell costimulation by TCR-CD28 microclusters and protein kinase C theta translocation. Immunity 29:589–601

    Article  CAS  PubMed  Google Scholar 

  • Zhang F, Marcus WD, Goyal NH, Selvaraj P, Springer TA, Zhu C (2005) Two-dimensional kinetics regulation of alphaLbeta2-ICAM-1 interaction by conformational changes of the alphaL-inserted domain. J Biol Chem 280:42207–42218

    Article  CAS  PubMed  Google Scholar 

  • Zhu DM, Dustin ML, Cairo CW, Thatte HS, Golan DE (2006) Mechanisms of cellular avidity regulation in CD2-CD58-mediated T cell adhesion. ACS Chem Biol 1:649–658

    Article  CAS  PubMed  Google Scholar 

  • Zhu DM, Dustin ML, Cairo CW, Golan DE (2007) Analysis of two-dimensional dissociation constant of laterally mobile cell adhesion molecules. Biophys J 92:1022–1034

    Article  CAS  PubMed  Google Scholar 

  • Zhu J, Luo BH, Xiao T, Zhang C, Nishida N, Springer TA (2008) Structure of a complete integrin ectodomain in a physiologic resting state and activation and deactivation by applied forces. Mol Cell 32:849–861

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

I thank the members of my lab who have contributed to many of the studies highlighted in this commentary. I thank Mike Sheetz for discussion of implications of bead size threshold for TCR stimulation.

Author information

Authors and Affiliations

  1. Helen L. and Martin S. Kimmel Center for Biology and Medicine in the Skirball Institute for Biomolecular Medicine and Department of Pathology, NYU School of Medicine, New York, NY, 10016, USA

    Michael L. Dustin

Authors
  1. Michael L. Dustin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael L. Dustin .

Editor information

Editors and Affiliations

  1. Allergy & Immunology, RIKEN Research Center for, Suehiro-cho 1-7-22, okohama City, Kanagawa, 230-0045, Japan

    Takashi Saito

  2. London Research Institute, Cancer Research UK, Lincoln's Inn Fields 44, London, WC2A 3PX, United Kingdom

    Facundo D. Batista

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Dustin, M.L. (2010). Insights into Function of the Immunological Synapse from Studies with Supported Planar Bilayers. In: Saito, T., Batista, F. (eds) Immunological Synapse. Current Topics in Microbiology and Immunology, vol 340. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-03858-7_1

Download citation

Publish with us

Policies and ethics

Search

Navigation