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Annual Review of Cell and Developmental Biology

Volume 32, 2016

Signaling and Polarized Communication Across the T Cell Immunological Synapse

Abstract

T cells express a somatically recombined antigen receptor (αβTCR) that is calibrated during development to respond to changes in peptides displayed by major histocompatibility complex proteins (pMHC) on the surface of antigen-presenting cells (APC). A key characteristic of pMHC for adaptive immunity is the ability to sample internal states of cells and tissues to sensitively detect changes associated with infection, cell derangement, or tissue injury. Physical T cell–APC contact sets up an axis for polarization of TCR, adhesion molecules, kinases, cytoskeletal elements, and organelles inherent in this mode of juxtacrine signaling. The discovery of further lateral organization of the TCR and adhesion molecules into radially symmetric compartments, the immunological synapse, revealed an intersecting plane of symmetry and potential for regulated symmetry breaking to control duration of T cell–APC interactions. In addition to organizing signaling machinery, the immunological synapse directs the polarized transport and secretion of cytokines and cytolytic agents across the synaptic cleft and is a site for the generation and exocytic release of bioactive microvesicles that can functionally affect recipient APC and other cells in the environment. This machinery is coopted by retroviruses, and human immune deficiency virus-1 may even use antigen-specific synapses for infection of healthy T cells. Here, we discuss recent advances in the molecular and cell biological mechanisms of immunological synapse assembly and signaling and its role in intercellular communication across the synaptic cleft.

Keyword(s): immunological synapse, microvesicles, polarization, signaling, T cell
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/content/journals/10.1146/annurev-cellbio-100814-125330
2016-10-06
2024-04-19
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Literature Cited

  1. Acton SE, Farrugia AJ, Astarita JL, Mourao-Sa D, Jenkins RP, Nye E. et al. 2014. Dendritic cells control fibroblastic reticular network tension and lymph node expansion. Nature 514:498–502 [Google Scholar]
  2. Andre P, Cambier JC, Wade TK, Raetz T, Wade WF. 1994. Distinct structural compartmentalization of the signal transducing functions of major histocompatibility complex class II (Ia) molecules. J. Exp. Med. 179:763–68 [Google Scholar]
  3. Arsenio J, Metz PJ, Chang JT. 2015. Asymmetric cell division in T lymphocyte fate diversification. Trends Immunol. 36:670–83 [Google Scholar]
  4. Astarita JL, Cremasco V, Fu J, Darnell MC, Peck JR. et al. 2015. The CLEC-2-podoplanin axis controls the contractility of fibroblastic reticular cells and lymph node microarchitecture. Nat. Immunol. 16:75–84 [Google Scholar]
  5. Babst M. 2011. MVB vesicle formation: ESCRT-dependent, ESCRT-independent and everything in between. Curr. Opin. Cell Biol. 23:452–57 [Google Scholar]
  6. Bachmann MF, McKall-Faienza K, Schmits R, Bouchard D, Beach J. et al. 1997. Distinct roles for LFA-1 and CD28 during activation of naive T cells: adhesion versus costimulation. Immunity 7:549–57 [Google Scholar]
  7. Bajenoff M, Egen JG, Koo LY, Laugier JP, Brau F. et al. 2006. Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes. Immunity 25:989–1001 [Google Scholar]
  8. Barda-Saad M, Braiman A, Titerence R, Bunnell SC, Barr VA, Samelson LE. 2005. Dynamic molecular interactions linking the T cell antigen receptor to the actin cytoskeleton. Nat. Immunol. 6:80–89 [Google Scholar]
  9. Bashour KT, Gondarenko A, Chen H, Shen K, Liu X. et al. 2014. CD28 and CD3 have complementary roles in T-cell traction forces. PNAS 111:2241–46 [Google Scholar]
  10. Batista FD, Iber D, Neuberger MS. 2001. B cells acquire antigen from target cells after synapse formation. Nature 411:489–94 [Google Scholar]
  11. Baumgartel V, Ivanchenko S, Dupont A, Sergeev M, Wiseman PW. et al. 2011. Live-cell visualization of dynamics of HIV budding site interactions with an ESCRT component. Nat. Cell Biol. 13:469–74 [Google Scholar]
  12. Berger EA, Murphy PM, Farber JM. 1999. Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu. Rev. Immunol. 17:657–700 [Google Scholar]
  13. Bertrand F, Muller S, Roh KH, Laurent C, Dupre L, Valitutti S. 2013. An initial and rapid step of lytic granule secretion precedes microtubule organizing center polarization at the cytotoxic T lymphocyte/target cell synapse. PNAS 110:6073–78 [Google Scholar]
  14. Biswas KH, Hartman KL, Yu CH, Harrison OJ, Song H. et al. 2015. E-cadherin junction formation involves an active kinetic nucleation process. PNAS 112:10932–37 [Google Scholar]
  15. Blanchard N, Lankar D, Faure F, Regnault A, Dumont C. et al. 2002. TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/ζ complex. J. Immunol. 168:3235–41 [Google Scholar]
  16. Boehm T, McCurley N, Sutoh Y, Schorpp M, Kasahara M, Cooper MD. 2012. VLR-based adaptive immunity. Annu. Rev. Immunol. 30:203–20 [Google Scholar]
  17. Bousso P, Bhakta NR, Lewis RS, Robey E. 2002. Dynamics of thymocyte–stromal cell interactions visualized by two-photon microscopy. Science 296:1876–80 [Google Scholar]
  18. Braun J, Fujiwara K, Pollard TD, Unanue ER. 1978. Two distinct mechanisms for redistribution of lymphocyte surface macromolecules. I. Relationship to cytoplasmic myosin. J. Cell Biol. 79:409–18 [Google Scholar]
  19. Brdicka T, Pavlistova D, Leo A, Bruyns E, Korinek V. et al. 2000. Phosphoprotein associated with glycosphingolipid-enriched microdomains (PAG), a novel ubiquitously expressed transmembrane adaptor protein, binds the protein tyrosine kinase Csk and is involved in regulation of T cell activation. J. Exp. Med. 191:1591–604 [Google Scholar]
  20. Brodovitch A, Limozin L, Bongrand P, Pierres A. 2015. Use of TIRF to monitor T-lymphocyte membrane dynamics with submicrometer and subsecond resolution. Cell. Mol. Bioeng. 8:178–86 [Google Scholar]
  21. Brown AC, Dobbie IM, Alakoskela JM, Davis I, Davis DM. 2012. Super-resolution imaging of remodeled synaptic actin reveals different synergies between NK cell receptors and integrins. Blood 120:3729–40 [Google Scholar]
  22. Bryant DM, Mostov KE. 2008. From cells to organs: building polarized tissue. Nat. Rev. Mol. Cell Biol. 9:887–901 [Google Scholar]
  23. Buchholz VR, Flossdorf M, Hensel I, Kretschmer L, Weissbrich B. et al. 2013. Disparate individual fates compose robust CD8+ T cell immunity. Science 340:630–35 [Google Scholar]
  24. Bufi N, Saitakis M, Dogniaux S, Buschinger O, Bohineust A. et al. 2015. Human primary immune cells exhibit distinct mechanical properties that are modified by inflammation. Biophys. J. 108:2181–90 [Google Scholar]
  25. Bunnell SC, Hong DI, Kardon JR, Yamazaki T, McGlade CJ. et al. 2002. T cell receptor ligation induces the formation of dynamically regulated signaling assemblies. J. Cell Biol. 158:1263–75 [Google Scholar]
  26. 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. 202:1031–36 [Google Scholar]
  27. Chang JT, Ciocca ML, Kinjyo I, Palanivel VR, McClurkin CE. et al. 2011. Asymmetric proteasome segregation as a mechanism for unequal partitioning of the transcription factor T-bet during T lymphocyte division. Immunity 34:492–504 [Google Scholar]
  28. Chang JT, Palanivel VR, Kinjyo I, Schambach F, Intlekofer AM. et al. 2007. Asymmetric T lymphocyte division in the initiation of adaptive immune responses. Science 315:1687–91 [Google Scholar]
  29. Chang VT, Fernandes RA, Ganzinger KA, Lee SF, Siebold C. et al. 2016. Initiation of T cell signaling by CD45 segregation at ‘close contacts’. Nat. Immunol. 17:574–82 [Google Scholar]
  30. Choudhuri K, Llodra J, Roth EW, Tsai J, Gordo S. et al. 2014. Polarized release of T-cell-receptor-enriched microvesicles at the immunological synapse. Nature 507:118–23 [Google Scholar]
  31. 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 436:578–82 [Google Scholar]
  32. Ciocca ML, Barnett BE, Burkhardt JK, Chang JT, Reiner SL. 2012. Cutting edge: asymmetric memory T cell division in response to rechallenge. J. Immunol. 188:4145–48 [Google Scholar]
  33. Clemente-Casares X, Blanco J, Ambalavanan P, Yamanouchi J, Singha S. et al. 2016. Expanding antigen-specific regulatory networks to treat autoimmunity. Nature 530:434–40 [Google Scholar]
  34. Cocucci E, Meldolesi J. 2015. Ectosomes and exosomes: shedding the confusion between extracellular vesicles. Trends Cell Biol. 25:364–72 [Google Scholar]
  35. Comrie WA, Li S, Boyle S, Burkhardt JK. 2015. The dendritic cell cytoskeleton promotes T cell adhesion and activation by constraining ICAM-1 mobility. J. Cell Biol. 208:457–73 [Google Scholar]
  36. Corbett AJ, Eckle SB, Birkinshaw RW, Liu L, Patel O. et al. 2014. T-cell activation by transitory neo-antigens derived from distinct microbial pathways. Nature 509:361–65 [Google Scholar]
  37. Cremasco V, Woodruff MC, Onder L, Cupovic J, Nieves-Bonilla JM. et al. 2014. B cell homeostasis and follicle confines are governed by fibroblastic reticular cells. Nat. Immunol. 15:973–81 [Google Scholar]
  38. Das DK, Feng Y, Mallis RJ, Li X, Keskin DB. et al. 2015. Force-dependent transition in the T-cell receptor beta-subunit allosterically regulates peptide discrimination and pMHC bond lifetime. PNAS 112:1517–22 [Google Scholar]
  39. Davis MM, Chien YH, Gascoigne NR, Hedrick SM. 1984. A murine T cell receptor gene complex: isolation, structure and rearrangement. Immunol. Rev. 81:235–58 [Google Scholar]
  40. Davis SJ, Van Der Merwe PA. 2006. The kinetic-segregation model: TCR triggering and beyond. Nat. Immunol. 7:803–9 [Google Scholar]
  41. De La Roche M, Ritter AT, Angus KL, Dinsmore C, Earnshaw CH. et al. 2013. Hedgehog signaling controls T cell killing at the immunological synapse. Science 342:1247–50 [Google Scholar]
  42. Deng L, Luo M, Velikovsky A, Mariuzza RA. 2013. Structural insights into the evolution of the adaptive immune system. Annu. Rev. Biophys. 42:191–215 [Google Scholar]
  43. Deng L, Velikovsky CA, Xu G, Iyer LM, Tasumi S. et al. 2010. A structural basis for antigen recognition by the T cell-like lymphocytes of sea lamprey. PNAS 107:13408–13 [Google Scholar]
  44. Dushek O, Goyette J, Van Der Merwe PA. 2012. Non-catalytic tyrosine-phosphorylated receptors. Immunol. Rev. 250:258–76 [Google Scholar]
  45. Dustin ML. 2007. Cell adhesion molecules and actin cytoskeleton at immune synapses and kinapses. Curr. Opin. Cell Biol. 19:529–33 [Google Scholar]
  46. Dustin ML, Bromley SK, Kan Z, Peterson DA, Unanue ER. 1997. Antigen receptor engagement delivers a stop signal to migrating T lymphocytes. PNAS 94:3909–13 [Google Scholar]
  47. Dustin ML, Colman DR. 2002. Neural and immunological synaptic relations. Science 298:785–89 [Google Scholar]
  48. Dustin ML, Olszowy MW, Holdorf AD, Li J, Bromley S. et al. 1998. A novel adaptor protein orchestrates receptor patterning and cytoskeletal polarity in T-cell contacts. Cell 94:667–77 [Google Scholar]
  49. Dustin ML, Springer TA. 1989. T cell receptor cross-linking transiently stimulates adhesiveness through LFA-1. Nature 341:619–24 [Google Scholar]
  50. Dustin ML, Starr T, Coombs D, Majeau GR, Meier W. et al. 2007. Quantification and modeling of tripartite CD2-, CD58FC chimera (Alefacept)-, and CD16-mediated cell adhesion. J. Biol. Chem. 282:34748–57 [Google Scholar]
  51. Esposito L, Hunter KM, Clark J, Rainbow DB, Stevens H. et al. 2014. Investigation of soluble and transmembrane CTLA-4 isoforms in serum and microvesicles. J. Immunol. 193:889–900 [Google Scholar]
  52. Finetti F, Paccani SR, Riparbelli MG, Giacomello E, Perinetti G. et al. 2009. Intraflagellar transport is required for polarized recycling of the TCR/CD3 complex to the immune synapse. Nat. Cell Biol. 11:1332–39 [Google Scholar]
  53. Freeman SA, Goyette J, Furuya W, Woods EC, Bertozzi CR. et al. 2016. Integrins form an expanding diffusional barrier that coordinates phagocytosis. Cell 164:128–40 [Google Scholar]
  54. Freiberg BA, Kupfer H, Maslanik W, Delli J, Kappler J. et al. 2002. Staging and resetting T cell activation in SMACs. Nat. Immunol. 3:911–17 [Google Scholar]
  55. Gagnon E, Schubert DA, Gordo S, Chu HH, Wucherpfennig KW. 2012. Local changes in lipid environment of TCR microclusters regulate membrane binding by the CD3ε cytoplasmic domain. J. Exp. Med. 209:2423–39 [Google Scholar]
  56. Geiger B, Rosen D, Berke G. 1982. Spatial relationships of microtubule-organizing centers and the contact area of cytotoxic T lymphocytes and target cells. J. Cell Biol. 95:137–43 [Google Scholar]
  57. Gerard A, Patino-Lopez G, Beemiller P, Nambiar R, Ben-Aissa K. et al. 2014. Detection of rare antigen-presenting cells through T cell–intrinsic meandering motility, mediated by Myo1g. Cell 158:492–505 [Google Scholar]
  58. Ghassemi S, Meacci G, Liu S, Gondarenko AA, Mathur A. et al. 2012. Cells test substrate rigidity by local contractions on submicrometer pillars. PNAS 109:5328–33 [Google Scholar]
  59. Graf B, Bushnell T, Miller J. 2007. LFA-1-mediated T cell costimulation through increased localization of TCR/class II complexes to the central supramolecular activation cluster and exclusion of CD45 from the immunological synapse. J. Immunol. 179:1616–24 [Google Scholar]
  60. Grakoui A, Bromley SK, Sumen C, Davis MM, Shaw AS. et al. 1999. The immunological synapse: a molecular machine controlling T cell activation. Science 285:221–27 [Google Scholar]
  61. Guy R, Ullrich SJ, Foo-Philips M, Hathcock KS, Appella E, Hodes RJ. 1989. Antigen-specific helper function of cell-free T cell products bearing TCR Vβ8 determinants. Science 244:1477–80 [Google Scholar]
  62. Hailman E, Burack WR, Shaw AS, Dustin ML, Allen PM. 2002. Immature CD4+CD8+ thymocytes form a multifocal immunological synapse with sustained tyrosine phosphorylation. Immunity 16:839–48 [Google Scholar]
  63. Harris TH, Banigan EJ, Christian DA, Konradt C, Tait Wojno ED. et al. 2012. Generalized Lévy walks and the role of chemokines in migration of effector CD8+ T cells. Nature 486:545–48 [Google Scholar]
  64. Hashimoto-Tane A, Yokosuka T, Sakata-Sogawa K, Sakuma M, Ishihara C. et al. 2011. Dynein-driven transport of T cell receptor microclusters regulates immune synapse formation and T cell activation. Immunity 34:919–31 [Google Scholar]
  65. Hirano M, Guo P, McCurley N, Schorpp M, Das S. et al. 2013. Evolutionary implications of a third lymphocyte lineage in lampreys. Nature 501:435–38 [Google Scholar]
  66. Holland SJ, Gao M, Hirano M, Iyer LM, Luo M. et al. 2014. Selection of the lamprey VLRC antigen receptor repertoire. PNAS 111:14834–39 [Google Scholar]
  67. Holt OJ, Gallo F, Griffiths GM. 2006. Regulating secretory lysosomes. J. Biochem. 140:7–12 [Google Scholar]
  68. Hui E, Vale RD. 2014. In vitro membrane reconstitution of the T-cell receptor proximal signaling network. Nat. Struct. Mol. Biol. 21:133–42 [Google Scholar]
  69. Hui KL, Balagopalan L, Samelson LE, Upadhyaya A. 2015. Cytoskeletal forces during signaling activation in Jurkat T-cells. Mol. Biol. Cell 26:685–95 [Google Scholar]
  70. Huppa JB, Axmann M, Mortelmaier MA, Lillemeier BF, Newell EW. et al. 2010. TCR-peptide-MHC interactions in situ show accelerated kinetics and increased affinity. Nature 463:963–67 [Google Scholar]
  71. Huse M, Klein LO, Girvin AT, Faraj JM, Li QJ. et al. 2007. Spatial and temporal dynamics of T cell receptor signaling with a photoactivatable agonist. Immunity 27:76–88 [Google Scholar]
  72. Huse M, Lillemeier BF, Kuhns MS, Chen DS, Davis MM. 2006. T cells use two directionally distinct pathways for cytokine secretion. Nat. Immunol. 7:247–55 [Google Scholar]
  73. Iezzi G, Scotet E, Scheidegger D, Lanzavecchia A. 1999. The interplay between the duration of TCR and cytokine signaling determines T cell polarization. Eur. J. Immunol. 29:4092–101 [Google Scholar]
  74. Irvine DJ, Purbhoo MA, Krogsgaard M, Davis MM. 2002. Direct observation of ligand recognition by T cells. Nature 419:845–49 [Google Scholar]
  75. James JR, Vale RD. 2012. Biophysical mechanism of T-cell receptor triggering in a reconstituted system. Nature 487:64–69 [Google Scholar]
  76. Jolly C, Welsch S, Michor S, Sattentau QJ. 2011. The regulated secretory pathway in CD4+ T cells contributes to human immunodeficiency virus type-1 cell-to-cell spread at the virological synapse. PLOS Pathog. 7:e1002226 [Google Scholar]
  77. Jönsson P, McColl J, Clarke RW, Ostanin VP, Jönsson B, Klenerman D. 2012. Hydrodynamic trapping of molecules in lipid bilayers. PNAS 109:10328–33 [Google Scholar]
  78. Jönsson P, Southcombe JH, Santos AM, Huo J, Fernandes RA. et al. 2016. Remarkably low affinity of CD4/peptide-major histocompatibility complex class II protein interactions. PNAS 113:5682–87 [Google Scholar]
  79. Jouvenet N, Zhadina M, Bieniasz PD, Simon SM. 2011. Dynamics of ESCRT protein recruitment during retroviral assembly. Nat. Cell Biol. 13:394–401 [Google Scholar]
  80. Judokusumo E, Tabdanov E, Kumari S, Dustin ML, Kam LC. 2012. Mechanosensing in T lymphocyte activation. Biophys. J. 102:L5–7 [Google Scholar]
  81. 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. 185:521–34 [Google Scholar]
  82. Kim JV, Kang SS, Dustin ML, McGavern DB. 2009. Myelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitis. Nature 457:191–95 [Google Scholar]
  83. Kosmrlj A, Read EL, Qi Y, Allen TM, Altfeld M. et al. 2010. Effects of thymic selection of the T-cell repertoire on HLA class I–associated control of HIV infection. Nature 465:350–54 [Google Scholar]
  84. Krummel MF, Macara I. 2006. Maintenance and modulation of T cell polarity. Nat. Immunol. 7:1143–49 [Google Scholar]
  85. Kuhn JR, Poenie M. 2002. Dynamic polarization of the microtubule cytoskeleton during CTL-mediated killing. Immunity 16:111–21 [Google Scholar]
  86. Kumari S, Depoil D, Martinelli R, Judokusumo E, Carmona G. et al. 2015. Actin foci facilitate activation of the phospholipase C-γ in primary T lymphocytes via the WASP pathway. eLife 4:e04953 [Google Scholar]
  87. Kupfer A, Singer SJ. 1989. The specific interaction of helper T cells and antigen-presenting B cells. IV. Membrane and cytoskeletal reorganizations in the bound T cell as a function of antigen dose. J. Exp. Med. 170:1697–713 [Google Scholar]
  88. Kupfer A, Singer SJ, Janeway CA Jr., Swain SL. 1987. Coclustering of CD4 (L3T4) molecule with the T-cell receptor is induced by specific direct interaction of helper T cells and antigen-presenting cells. PNAS 84:5888–92 [Google Scholar]
  89. Kusumi A, Nakada C, Ritchie K, Murase K, Suzuki K. et al. 2005. Paradigm shift of the plasma membrane concept from the two-dimensional continuum fluid to the partitioned fluid: high-speed single-molecule tracking of membrane molecules. Annu. Rev. Biophys. Biomol. Struct. 34:351–78 [Google Scholar]
  90. Lang P, Stolpa JC, Freiberg BA, Crawford F, Kappler J. et al. 2001. TCR-induced transmembrane signaling by peptide/MHC class II via associated Ig-α/β dimers. Science 291:1537–40 [Google Scholar]
  91. Lemaitre F, Moreau HD, Vedele L, Bousso P. 2013. Phenotypic CD8+ T cell diversification occurs before, during, and after the first T cell division. J. Immunol. 191:1578–85 [Google Scholar]
  92. Lillemeier BF, Pfeiffer JR, Surviladze Z, Wilson BS, Davis MM. 2006. Plasma membrane–associated proteins are clustered into islands attached to the cytoskeleton. PNAS 103:18992–97 [Google Scholar]
  93. Little AM, Parham P. 1999. Polymorphism and evolution of HLA class I and II genes and molecules. Rev. Immunogenet. 1:105–23 [Google Scholar]
  94. Liu B, Chen W, Evavold BD, Zhu C. 2014. Accumulation of dynamic catch bonds between TCR and agonist peptide-MHC triggers T cell signaling. Cell 157:357–68 [Google Scholar]
  95. Liu Y, Blanchfield L, Ma VP, Andargachew R, Galior K. et al. 2016. DNA-based nanoparticle tension sensors reveal that T-cell receptors transmit defined pN forces to their antigens for enhanced fidelity. PNAS 113:5610–15 [Google Scholar]
  96. Malhotra D, Fletcher AL, Astarita J, Lukacs-Kornek V, Tayalia P. et al. 2012. Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks. Nat. Immunol. 13:499–510 [Google Scholar]
  97. Marshall MR, Pattu V, Halimani M, Maier-Peuschel M, Muller ML. et al. 2015. VAMP8-dependent fusion of recycling endosomes with the plasma membrane facilitates T lymphocyte cytotoxicity. J. Cell Biol. 210:135–51 [Google Scholar]
  98. Martinez-Martin N, Fernandez-Arenas E, Cemerski S, Delgado P, Turner M. et al. 2011. T cell receptor internalization from the immunological synapse is mediated by TC21 and RhoG GTPase–dependent phagocytosis. Immunity 35:208–22 [Google Scholar]
  99. McConnell HM, Watts TH, Weis RM, Brian AA. 1986. Supported planar membranes in studies of cell-cell recognition in the immune system. Biochim. Biophys. Acta 864:95–106 [Google Scholar]
  100. McCullough J, Colf LA, Sundquist WI. 2013. Membrane fission reactions of the mammalian ESCRT pathway. Annu. Rev. Biochem. 82:663–92 [Google Scholar]
  101. Mempel TR, Henrickson SE, Von Andrian UH. 2004. T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases. Nature 427:154–59 [Google Scholar]
  102. Mescher MF. 1992. Surface contact requirements for activation of cytotoxic T lymphocytes. J. Immunol. 149:2402–5 [Google Scholar]
  103. Miller MJ, Wei SH, Parker I, Cahalan MD. 2002. Two-photon imaging of lymphocyte motility and antigen response in intact lymph node. Science 296:1869–73 [Google Scholar]
  104. Mittelbrunn M, Gutierrez-Vazquez C, Villarroya-Beltri C, Gonzalez S, Sanchez-Cabo F. et al. 2011. Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat. Commun. 2:282 [Google Scholar]
  105. 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 [Google Scholar]
  106. Monks CR, Kupfer H, Tamir I, Barlow A, Kupfer A. 1997. Selective modulation of protein kinase C-θ during T-cell activation. Nature 385:83–86 [Google Scholar]
  107. Monroe JG, Cambier JC. 1983. B cell activation. III. B cell plasma membrane depolarization and hyper-Ia antigen expression induced by receptor immunoglobulin cross-linking are coupled. J. Exp. Med. 158:1589–99 [Google Scholar]
  108. Negulescu PA, Krasieva TB, Khan A, Kerschbaum HH, Cahalan MD. 1996. Polarity of T cell shape, motility, and sensitivity to antigen. Immunity 4:421–30 [Google Scholar]
  109. Nelson WJ. 2003. Adaptation of core mechanisms to generate cell polarity. Nature 422:766–74 [Google Scholar]
  110. O'Connor RS, Hao X, Shen K, Bashour K, Akimova T. et al. 2012. Substrate rigidity regulates human T cell activation and proliferation. J. Immunol. 189:1330–39 [Google Scholar]
  111. O'Donoghue GP, Pielak RM, Smoligovets AA, Lin JJ, Groves JT. 2013. Direct single molecule measurement of TCR triggering by agonist pMHC in living primary T cells. eLife 2:e00778 [Google Scholar]
  112. O'Hara RM Jr. 1995. Antigen-specific suppressor factor: missing pieces in the puzzle. Immunol. Res. 14:252–62 [Google Scholar]
  113. Oh-Hora M. 2009. Calcium signaling in the development and function of T-lineage cells. Immunol. Rev. 231:210–24 [Google Scholar]
  114. Okoye IS, Coomes SM, Pelly VS, Czieso S, Papayannopoulos V. et al. 2014. MicroRNA-containing T-regulatory-cell-derived exosomes suppress pathogenic T helper 1 cells. Immunity 41:89–103 [Google Scholar]
  115. Penna A, Demuro A, Yeromin AV, Zhang SL, Safrina O. et al. 2008. The CRAC channel consists of a tetramer formed by Stim-induced dimerization of Orai dimers. Nature 456:116–20 [Google Scholar]
  116. Peters PJ, Geuze HJ, Van Der Donk HA, Slot JW, Griffith JM. et al. 1989. Molecules relevant for T cell–target cell interaction are present in cytolytic granules of human T lymphocytes. Eur. J. Immunol. 19:1469–75 [Google Scholar]
  117. Piguet V, Sattentau Q. 2004. Dangerous liaisons at the virological synapse. J. Clin. Investig. 114:605–10 [Google Scholar]
  118. Poo WJ, Conrad L, Janeway CA Jr. 1988. Receptor-directed focusing of lymphokine release by helper T cells. Nature 332:378–80 [Google Scholar]
  119. Purbhoo MA, Irvine DJ, Huppa JB, Davis MM. 2004. T cell killing does not require the formation of a stable mature immunological synapse. Nat. Immunol. 5:524–30 [Google Scholar]
  120. Richie LI, Ebert PJ, Wu LC, Krummel MF, Owen JJ, Davis MM. 2002. Imaging synapse formation during thymocyte selection: inability of CD3ζ to form a stable central accumulation during negative selection. Immunity 16:595–606 [Google Scholar]
  121. Ritter AT, Asano Y, Stinchcombe JC, Dieckmann NM, Chen BC. et al. 2015. Actin depletion initiates events leading to granule secretion at the immunological synapse. Immunity 42:864–76 [Google Scholar]
  122. Russell S. 2008. How polarity shapes the destiny of T cells. J. Cell Sci. 121:131–36 [Google Scholar]
  123. Sage PT, Varghese LM, Martinelli R, Sciuto TE, Kamei M. et al. 2012. Antigen recognition is facilitated by invadosome-like protrusions formed by memory/effector T cells. J. Immunol. 188:3686–99 [Google Scholar]
  124. Samelson LE. 2002. Signal transduction mediated by the T cell antigen receptor: the role of adapter proteins. Annu. Rev. Immunol. 20:371–94 [Google Scholar]
  125. Sandstrom A, Peigne CM, Leger A, Crooks JE, Konczak F. et al. 2014. The intracellular B30.2 domain of butyrophilin 3A1 binds phosphoantigens to mediate activation of human Vγ9Vδ2 T cells. Immunity 40:490–500 [Google Scholar]
  126. Schmid EM, Bakalar MH, Choudhuri K, Weichsel J, Ann HS. et al. 2016. Size-dependent protein segregation at membrane interfaces. Nat. Phys. 12:704–11 [Google Scholar]
  127. Shi X, Bi Y, Yang W, Guo X, Jiang Y. et al. 2013. Ca2+ regulates T-cell receptor activation by modulating the charge property of lipids. Nature 493:111–15 [Google Scholar]
  128. Sims TN, Soos TJ, Xenias HS, Dubin-Thaler B, Hofman JM. et al. 2007. Opposing effects of PKCθ and WASp on symmetry breaking and relocation of the immunological synapse. Cell 129:773–85 [Google Scholar]
  129. Singla V, Reiter JF. 2006. The primary cilium as the cell's antenna: signaling at a sensory organelle. Science 313:629–33 [Google Scholar]
  130. Skokos D, Shakhar G, Varma R, Waite JC, Cameron TO. et al. 2007. Peptide-MHC potency governs dynamic interactions between T cells and dendritic cells in lymph nodes. Nat. Immunol. 8:835–44 [Google Scholar]
  131. Soares H, Henriques R, Sachse M, Ventimiglia L, Alonso MA. et al. 2013. Regulated vesicle fusion generates signaling nanoterritories that control T cell activation at the immunological synapse. J. Exp. Med. 210:2415–33 [Google Scholar]
  132. Springer TA. 1990. Adhesion receptors of the immune system. Nature 346:425–34 [Google Scholar]
  133. Stepanek O, Prabhakar AS, Osswald C, King CG, Bulek A. et al. 2014. Coreceptor scanning by the T cell receptor provides a mechanism for T cell tolerance. Cell 159:333–45 [Google Scholar]
  134. Stinchcombe JC, Majorovits E, Bossi G, Fuller S, Griffiths GM. 2006. Centrosome polarization delivers secretory granules to the immunological synapse. Nature 443:462–65 [Google Scholar]
  135. Su X, Ditlev JA, Hui E, Xing W, Banjade S. et al. 2016. Phase separation of signaling molecules promotes T cell receptor signal transduction. Science 352:595–99 [Google Scholar]
  136. Tabdanov E, Gondarenko S, Kumari S, Liapis A, Dustin ML. et al. 2015. Micropatterning of TCR and LFA-1 ligands reveals complementary effects on cytoskeleton mechanics in T cells. Integr. Biol. 7:1272–84
  137. Tan YX, Manz BN, Freedman TS, Zhang C, Shokat KM, Weiss A. 2014. Inhibition of the kinase Csk in thymocytes reveals a requirement for actin remodeling in the initiation of full TCR signaling. Nat. Immunol. 15:186–94 [Google Scholar]
  138. Trappmann B, Gautrot JE, Connelly JT, Strange DG, Li Y. et al. 2012. Extracellular-matrix tethering regulates stem-cell fate. Nat. Mater. 11:642–49 [Google Scholar]
  139. 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 Cθ. J. Immunol. 181:4852–63 [Google Scholar]
  140. Valitutti S, Dessing M, Aktories K, Gallati H, Lanzavecchia A. 1995. Sustained signaling leading to T cell activation results from prolonged T cell receptor occupancy. Role of T cell actin cytoskeleton. J. Exp. Med. 181:577–84 [Google Scholar]
  141. Vardhana S, Choudhuri K, Varma R, Dustin ML. 2010. Essential role of ubiquitin and TSG101 protein in formation and function of the central supramolecular activation cluster. Immunity 32:531–40 [Google Scholar]
  142. 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 25:117–27 [Google Scholar]
  143. Vasiliver-Shamis G, Cho MW, Hioe CE, Dustin ML. 2009. Human immunodeficiency virus type 1 envelope gp120-induced partial T-cell receptor signaling creates an F-actin-depleted zone in the virological synapse. J. Virol. 83:11341–55 [Google Scholar]
  144. Vasiliver-Shamis G, Dustin ML, Hioe CE. 2010. HIV-1 virological synapse is not simply a copycat of the immunological synapse. Viruses 2:1239–60 [Google Scholar]
  145. Verbist KC, Guy CS, Milasta S, Liedmann S, Kaminski MM. et al. 2016. Metabolic maintenance of cell asymmetry following division in activated T lymphocytes. Nature 532:389–93 [Google Scholar]
  146. Von Schwedler UK, Stuchell M, Muller B, Ward DM, Chung HY. et al. 2003. The protein network of HIV budding. Cell 114:701–13 [Google Scholar]
  147. Waite JC, Vardhana S, Shaw PJ, Jang JE, McCarl CA. et al. 2013. Interference with Ca2+ release activated Ca2+ (CRAC) channel function delays T-cell arrest in vivo. Eur. J. Immunol. 43:3343–54 [Google Scholar]
  148. Weiss A. 2010. The right team at the right time to go for a home run: tyrosine kinase activation by the TCR. Nat. Immunol. 11:101–4 [Google Scholar]
  149. Wild MK, Cambiaggi A, Brown MH, Davies EA, Ohno H. et al. 1999. Dependence of T cell antigen recognition on the dimensions of an accessory receptor-ligand complex. J. Exp. Med. 190:31–41 [Google Scholar]
  150. Wilson BS, Steinberg SL, Liederman K, Pfeiffer JR, Surviladze Z. et al. 2004. Markers for detergent-resistant lipid rafts occupy distinct and dynamic domains in native membranes. Mol. Biol. Cell 15:2580–92 [Google Scholar]
  151. Woolf E, Grigorova I, Sagiv A, Grabovsky V, Feigelson SW. et al. 2007. Lymph node chemokines promote sustained T lymphocyte motility without triggering stable integrin adhesiveness in the absence of shear forces. Nat. Immunol. 8:1076–85 [Google Scholar]
  152. Worbs T, Mempel TR, Bolter J, Von Andrian UH, Forster R. 2007. CCR7 ligands stimulate the intranodal motility of T lymphocytes in vivo. J. Exp. Med. 204:489–95 [Google Scholar]
  153. Xu C, Gagnon E, Call ME, Schnell JR, Schwieters CD. et al. 2008. Regulation of T cell receptor activation by dynamic membrane binding of the CD3ε cytoplasmic tyrosine-based motif. Cell 135:702–13 [Google Scholar]
  154. Yang H, Gou X, Wang Y, Fahmy TM, Leung AY. et al. 2015. A dynamic model of chemoattractant-induced cell migration. Biophys. J. 108:1645–51 [Google Scholar]
  155. Yi J, Wu X, Chung AH, Chen JK, Kapoor TM, Hammer JA. 2013. Centrosome repositioning in T cells is biphasic and driven by microtubule end-on capture-shrinkage. J. Cell Biol. 202:779–92 [Google Scholar]
  156. 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 32:849–61 [Google Scholar]
/content/journals/10.1146/annurev-cellbio-100814-125330
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Signaling and Polarized Communication Across the T Cell Immunological Synapse
Annual Review of Cell and Developmental Biology 32, 303 (2016); https://doi.org/10.1146/annurev-cellbio-100814-125330
/content/journals/10.1146/annurev-cellbio-100814-125330
/content/journals/10.1146/annurev-cellbio-100814-125330
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