{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T12:24:02Z","timestamp":1778156642505,"version":"3.51.4"},"reference-count":79,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2003,12,1]],"date-time":"2003-12-01T00:00:00Z","timestamp":1070236800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nat Rev Immunol"],"published-print":{"date-parts":[[2003,12]]},"DOI":"10.1038\/nri1245","type":"journal-article","created":{"date-parts":[[2003,12,1]],"date-time":"2003-12-01T19:11:35Z","timestamp":1070305895000},"page":"973-983","source":"Crossref","is-referenced-by-count":499,"title":["T-cell-antigen recognition and the immunological synapse"],"prefix":"10.1038","volume":"3","author":[{"given":"Johannes B.","family":"Huppa","sequence":"first","affiliation":[]},{"given":"Mark M.","family":"Davis","sequence":"additional","affiliation":[]}],"member":"297","reference":[{"key":"BFnri1245_CR1","first-page":"113","volume":"135D","author":"MA Norcross","year":"1984","unstructured":"Norcross, M. A. A synaptic basis for T-lymphocyte activation. Ann. Immunol. (Paris) 135D, 113\u2013134 (1984).","journal-title":"Ann. Immunol. (Paris)"},{"key":"BFnri1245_CR2","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1111\/j.1749-6632.1987.tb51284.x","volume":"505","author":"WE Paul","year":"1987","unstructured":"Paul, W. E. et al. Regulation of B-lymphocyte activation, proliferation, and differentiation. Ann. NY Acad. Sci. 505, 82\u201389 (1987).","journal-title":"Ann. NY Acad. Sci."},{"key":"BFnri1245_CR3","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1083\/jcb.99.5.1575","volume":"99","author":"S Spiegel","year":"1984","unstructured":"Spiegel, S., Kassis, S., Wilchek, M. & Fishman, P. H. Direct visualization of redistribution and capping of fluorescent gangliosides on lymphocytes. J. Cell Biol. 99, 1575\u20131581 (1984).","journal-title":"J. Cell Biol."},{"key":"BFnri1245_CR4","doi-asserted-by":"publisher","first-page":"7224","DOI":"10.1073\/pnas.80.23.7224","volume":"80","author":"A Kupfer","year":"1983","unstructured":"Kupfer, A., Dennert, G. & Singer, S. J. Polarization of the Golgi apparatus and the microtubule-organizing center within cloned natural killer cells bound to their targets. Proc. Natl Acad. Sci. USA 80, 7224\u20137228 (1983).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnri1245_CR5","doi-asserted-by":"crossref","first-page":"2762","DOI":"10.4049\/jimmunol.133.5.2762","volume":"133","author":"A Kupfer","year":"1984","unstructured":"Kupfer, A. & Dennert, G. Reorientation of the microtubule-organizing center and the Golgi apparatus in cloned cytotoxic lymphocytes triggered by binding to lysable target cells. J. Immunol. 133, 2762\u20132766 (1984).","journal-title":"J. Immunol."},{"key":"BFnri1245_CR6","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1084\/jem.181.2.577","volume":"181","author":"S Valitutti","year":"1995","unstructured":"Valitutti, S., Dessing, M., Aktories, K., Gallati, H. & Lanzavecchia, A. 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\u2013584 (1995).","journal-title":"J. Exp. Med."},{"key":"BFnri1245_CR7","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1038\/25764","volume":"395","author":"CR Monks","year":"1998","unstructured":"Monks, C. R., Freiberg, B. A., Kupfer, H., Sciaky, N. & Kupfer, A. Three-dimensional segregation of supramolecular activation clusters in T cells. Nature 395, 82\u201386 (1998). This landmark study showed the presence of supra-molecular activation complexes (SMACs) within the immune synapse.","journal-title":"Nature"},{"key":"BFnri1245_CR8","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1016\/S0960-9822(00)00130-5","volume":"4","author":"E Donnadieu","year":"1994","unstructured":"Donnadieu, E., Bismuth, G. & Trautmann, A. Antigen recognition by helper T cells elicits a sequence of distinct changes of their shape and intracellular calcium. Curr. Biol. 4, 584\u2013595 (1994).","journal-title":"Curr. Biol."},{"key":"BFnri1245_CR9","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/S1074-7613(00)80409-4","volume":"4","author":"PA Negulescu","year":"1996","unstructured":"Negulescu, P. A., Krasieva, T. B., Khan, A., Kerschbaum, H. H. & Cahalan, M. D. Polarity of T cell shape, motility, and sensitivity to antigen. Immunity 4, 421\u2013430 (1996).","journal-title":"Immunity"},{"key":"BFnri1245_CR10","doi-asserted-by":"publisher","first-page":"6302","DOI":"10.1073\/pnas.95.11.6302","volume":"95","author":"C Wulfing","year":"1998","unstructured":"Wulfing, C., Sjaastad, M. D. & Davis, M. M. 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. Proc. Natl Acad. Sci. USA 95, 6302\u20136307 (1998).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnri1245_CR11","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1016\/S0092-8674(00)81608-6","volume":"94","author":"ML Dustin","year":"1998","unstructured":"Dustin, M. L. et al. A novel adaptor protein orchestrates receptor patterning and cytoskeletal polarity in T-cell contacts. Cell 94, 667\u2013677 (1998).","journal-title":"Cell"},{"key":"BFnri1245_CR12","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1126\/science.285.5425.221","volume":"285","author":"A Grakoui","year":"1999","unstructured":"Grakoui, A. et al. The immunological synapse: a molecular machine controlling T cell activation. Science 285, 221\u2013227 (1999). These authors were the first to use supported lipid bilayers as artifical antigen-presenting cells (APCs) to monitor the spatial\u2013temporal redistribution of peptide\u2013MHC complexes and intercellular adhesion molecule 1 (ICAM1) during the development of the immune synapse.","journal-title":"Science"},{"key":"BFnri1245_CR13","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1038\/346574a0","volume":"346","author":"CV Harding","year":"1990","unstructured":"Harding, C. V. & Unanue, E. R. Quantitation of antigen-presenting cell MHC class II\/peptide complexes necessary for T-cell stimulation. Nature 346, 574\u2013576 (1990).","journal-title":"Nature"},{"key":"BFnri1245_CR14","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1126\/science.2118680","volume":"249","author":"S Demotz","year":"1990","unstructured":"Demotz, S., Grey, H. M. & Sette, A. The minimal number of class II MHC-antigen complexes needed for T cell activation. Science 249, 1028\u20131030 (1990).","journal-title":"Science"},{"key":"BFnri1245_CR15","doi-asserted-by":"publisher","first-page":"3310","DOI":"10.1002\/eji.1830271230","volume":"27","author":"K Kimachi","year":"1997","unstructured":"Kimachi, K., Croft, M. & Grey, H. M. The minimal number of antigen-major histocompatibility complex class II complexes required for activation of naive and primed T cells. Eur. J. Immunol. 27, 3310\u20133317 (1997).","journal-title":"Eur. J. Immunol."},{"key":"BFnri1245_CR16","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1038\/nature01076","volume":"419","author":"DJ Irvine","year":"2002","unstructured":"Irvine, D. J., Purbhoo, M. A., Krogsgaard, M. & Davis, M. M. Direct observation of ligand recognition by T cells. Nature 419, 845\u2013849 (2002). This paper provided direct evidence that effector T cells respond to a single stimulatory peptide\u2013MHC complex and that CD4 is required for this degree of sensitivity.","journal-title":"Nature"},{"key":"BFnri1245_CR17","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1006\/jmbi.1996.0547","volume":"262","author":"WR Chang","year":"1996","unstructured":"Chang, W. R. et al. Crystal structure of R-phycoerythrin from Polysiphonia urceolata at 2. 8 A resolution. J. Mol. Biol. 262, 721\u2013731 (1996).","journal-title":"J. Mol. Biol."},{"key":"BFnri1245_CR18","doi-asserted-by":"publisher","first-page":"4087","DOI":"10.1073\/pnas.86.11.4087","volume":"86","author":"K Peck","year":"1989","unstructured":"Peck, K., Stryer, L., Glazer, A. N. & Mathies, R. A. Single-molecule fluorescence detection: autocorrelation criterion and experimental realization with phycoerythrin. Proc. Natl Acad. Sci. USA 86, 4087\u20134091 (1989).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnri1245_CR19","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1038\/86318","volume":"2","author":"S Feske","year":"2001","unstructured":"Feske, S., Giltnane, J., Dolmetsch, R., Staudt, L. M. & Rao, A. Gene regulation mediated by calcium signals in T lymphocytes. Nature Immunol. 2, 316\u2013324 (2001).","journal-title":"Nature Immunol."},{"key":"BFnri1245_CR20","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/S1074-7613(00)80629-9","volume":"9","author":"JJ Boniface","year":"1998","unstructured":"Boniface, J. J. et al. Initiation of signal transduction through the T cell receptor requires the multivalent engagement of peptide\/MHC ligands. Immunity 9, 459\u2013466 (1998).","journal-title":"Immunity"},{"key":"BFnri1245_CR21","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/S1074-7613(00)80177-6","volume":"12","author":"JR Cochran","year":"2000","unstructured":"Cochran, J. R., Cameron, T. O. & Stern, L. J. The relationship of MHC-peptide binding and T cell activation probed using chemically defined MHC class II oligomers. Immunity 12, 241\u2013250 (2000).","journal-title":"Immunity"},{"key":"BFnri1245_CR22","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1002\/eji.200323844","volume":"33","author":"C Randriamampita","year":"2003","unstructured":"Randriamampita, C., Boulla, G., Revy, P., Lemaitre, F. & Trautmann, A. T cell adhesion lowers the threshold for antigen detection. Eur. J. Immunol. 33, 1215\u20131223 (2003).","journal-title":"Eur. J. Immunol."},{"key":"BFnri1245_CR23","doi-asserted-by":"publisher","first-page":"26983","DOI":"10.1074\/jbc.M302709200","volume":"278","author":"MA Doucey","year":"2003","unstructured":"Doucey, M. A. et al. The \u03b21 and \u03b23 integrins promote T cell receptor-mediated cytotoxic T lymphocyte activation. J. Biol. Chem. 278, 26983\u201326991 (2003).","journal-title":"J. Biol. Chem."},{"key":"BFnri1245_CR24","doi-asserted-by":"publisher","first-page":"13729","DOI":"10.1073\/pnas.212515299","volume":"99","author":"Q Ge","year":"2002","unstructured":"Ge, Q. et al. Soluble peptide\u2013MHC monomers cause activation of CD8+ T cells through transfer of the peptide to T cell MHC molecules. Proc. Natl Acad. Sci. USA 99, 13729\u201313734 (2002).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnri1245_CR25","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1146\/annurev.iy.07.040189.001521","volume":"7","author":"A Kupfer","year":"1989","unstructured":"Kupfer, A. & Singer, S. J. Cell biology of cytotoxic and helper T cell functions: immunofluorescence microscopic studies of single cells and cell couples. Annu. Rev. Immunol. 7, 309\u201337 (1989).","journal-title":"Annu. Rev. Immunol."},{"key":"BFnri1245_CR26","doi-asserted-by":"publisher","first-page":"2266","DOI":"10.1126\/science.282.5397.2266","volume":"282","author":"C Wulfing","year":"1998","unstructured":"Wulfing, C. & Davis, M. M. A receptor\/cytoskeletal movement triggered by co-stimulation during T cell activation. Science 282, 2266\u20132269 (1998). This paper indicated that co-stimulation is required for cytoskeleton-driven mass transport of lipids (and probably proteins) from the rear end of the T cell to the immune synapse.","journal-title":"Science"},{"key":"BFnri1245_CR27","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1126\/science.283.5402.680","volume":"283","author":"A Viola","year":"1999","unstructured":"Viola, A., Schroeder, S., Sakakibara, Y. & Lanzavecchia, A. T lymphocyte co-stimulation mediated by reorganization of membrane microdomains. Science 283, 680\u2013682 (1999).","journal-title":"Science"},{"key":"BFnri1245_CR28","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1038\/ni741","volume":"3","author":"C Wulfing","year":"2002","unstructured":"Wulfing, C. et al. Co-stimulation and endogenous MHC ligands contribute to T cell recognition. Nature Immunol. 3, 42\u201327 (2002).","journal-title":"Nature Immunol."},{"key":"BFnri1245_CR29","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/0167-5699(96)80617-7","volume":"17","author":"SJ Davis","year":"1996","unstructured":"Davis, S. J. & van der Merwe, P. A. The structure and ligand interactions of CD2: implications for T-cell function. Immunol. Today 17, 177\u2013187 (1996).","journal-title":"Immunol. Today"},{"key":"BFnri1245_CR30","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/S1074-7613(00)80279-4","volume":"6","author":"AS Shaw","year":"1997","unstructured":"Shaw, A. S. & Dustin, M. L. Making the T cell receptor go the distance: a topological view of T cell activation. Immunity 6, 361\u2013369 (1997).","journal-title":"Immunity"},{"key":"BFnri1245_CR31","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1084\/jem.190.1.31","volume":"190","author":"MK Wild","year":"1999","unstructured":"Wild, M. K. et al. Dependence of T cell antigen recognition on the dimensions of an accessory receptor\u2013ligand complex. J. Exp. Med. 190, 31\u201341 (1999).","journal-title":"J. Exp. Med."},{"key":"BFnri1245_CR32","doi-asserted-by":"publisher","first-page":"6548","DOI":"10.1073\/pnas.111536798","volume":"98","author":"SY Qi","year":"2001","unstructured":"Qi, S. Y., Groves, J. T. & Chakraborty, A. K. Synaptic pattern formation during cellular recognition. Proc. Natl Acad. Sci. USA 98, 6548\u20136553 (2001).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnri1245_CR33","doi-asserted-by":"publisher","first-page":"1784","DOI":"10.1016\/S0006-3495(02)73944-1","volume":"83","author":"NJ Burroughs","year":"2002","unstructured":"Burroughs, N. J. & Wulfing, C. Differential segregation in a cell\u2013cell contact interface: the dynamics of the immunological synapse. Biophys. J. 83, 1784\u20131796 (2002).","journal-title":"Biophys. J."},{"key":"BFnri1245_CR34","doi-asserted-by":"publisher","first-page":"10138","DOI":"10.1073\/pnas.97.18.10138","volume":"97","author":"KG >Johnson","year":"2000","unstructured":"&gt;Johnson, K. G., Bromley, S. K., Dustin, M. L. & Thomas, M. L. A supramolecular basis for CD45 tyrosine phosphatase regulation in sustained T cell activation. Proc. Natl Acad. Sci. USA 97, 10138\u201310143 (2000).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnri1245_CR35","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/S0960-9822(00)00362-6","volume":"10","author":"O Leupin","year":"2000","unstructured":"Leupin, O., Zaru, R., Laroche, T., Muller, S. & Valitutti, S. Exclusion of CD45 from the T-cell receptor signaling area in antigen-stimulated T lymphocytes. Curr. Biol. 10, 277\u2013280 (2000).","journal-title":"Curr. Biol."},{"key":"BFnri1245_CR36","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1038\/ni836","volume":"3","author":"BA Freiberg","year":"2002","unstructured":"Freiberg, B. A. et al. Staging and resetting T cell activation in SMACs. Nature Immunol. 3, 911\u2013917 (2002).","journal-title":"Nature Immunol."},{"key":"BFnri1245_CR37","doi-asserted-by":"crossref","first-page":"6459","DOI":"10.4049\/jimmunol.161.12.6459","volume":"161","author":"AI Sperling","year":"1998","unstructured":"Sperling, A. I. et al. TCR signaling induces selective exclusion of CD43 from the T cell-antigen-presenting cell contact site. J. Immunol. 161, 6459\u20136462 (1998).","journal-title":"J. Immunol."},{"key":"BFnri1245_CR38","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1016\/S1074-7613(01)00225-4","volume":"15","author":"A Roumier","year":"2001","unstructured":"Roumier, A. et al. The membrane-microfilament linker ezrin is involved in the formation of the immunological synapse and in T cell activation. Immunity 15, 715\u2013728 (2001).","journal-title":"Immunity"},{"key":"BFnri1245_CR39","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/S1074-7613(01)00231-X","volume":"15","author":"J Delon","year":"2001","unstructured":"Delon, J., Kaibuchi, K. & Germain, R. N. Exclusion of CD43 from the immunological synapse is mediated by phosphorylation-regulated relocation of the cytoskeletal adaptor moesin. Immunity 15, 691\u2013701 (2001).","journal-title":"Immunity"},{"key":"BFnri1245_CR40","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/S1074-7613(01)00224-2","volume":"15","author":"EJ Allenspach","year":"2001","unstructured":"Allenspach, E. J. et al. ERM-dependent movement of CD43 defines a novel protein complex distal to the immunological synapse. Immunity 15, 739\u2013750 (2001).","journal-title":"Immunity"},{"key":"BFnri1245_CR41","doi-asserted-by":"publisher","first-page":"3740","DOI":"10.4049\/jimmunol.168.8.3740","volume":"168","author":"ND Savage","year":"2002","unstructured":"Savage, N. D. et al. Polar redistribution of the sialoglycoprotein CD43: implications for T cell function. J. Immunol. 168, 3740\u20133746 (2002).","journal-title":"J. Immunol."},{"key":"BFnri1245_CR42","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.1126\/science.1056594","volume":"292","author":"AA Khan","year":"2001","unstructured":"Khan, A. A., Bose, C., Yam, L. S., Soloski, M. J. & Rupp, F. Physiological regulation of the immunological synapse by agrin. Science 292, 1681\u20131686 (2001).","journal-title":"Science"},{"key":"BFnri1245_CR43","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1038\/35055582","volume":"409","author":"M Demetriou","year":"2001","unstructured":"Demetriou, M., Granovsky, M., Quaggin, S. & Dennis, J. W. Negative regulation of T-cell activation and autoimmunity by Mgat5 N-glycosylation. Nature 409, 733\u2013739 (2001).","journal-title":"Nature"},{"key":"BFnri1245_CR44","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1126\/science.289.5483.1349","volume":"289","author":"MF Krummel","year":"2000","unstructured":"Krummel, M. F., Sjaastad, M. D., Wulfing, C. & Davis, M. M. Differential clustering of CD4 and CD3\u03b6 during T cell recognition. Science 289, 1349\u20131352 (2000). This study showed that the T-cell receptor (TCR) and CD4 do not act together at all times during T-cell-antigen recognition, as they have a different distribution within the immune synapse at later stages.","journal-title":"Science"},{"key":"BFnri1245_CR45","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/S1074-7613(02)00301-1","volume":"16","author":"T Zal","year":"2002","unstructured":"Zal, T., Zal, M. A. & Gascoigne, N. R. Inhibition of T cell receptor\u2013coreceptor interactions by antagonist ligands visualized by live FRET imaging of the T-hybridoma immunological synapse. Immunity 16, 521\u2013534 (2002).","journal-title":"Immunity"},{"key":"BFnri1245_CR46","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1083\/jcb.143.3.613","volume":"143","author":"J Sloan-Lancaster","year":"1998","unstructured":"Sloan-Lancaster, J. et al. ZAP-70 association with T cell receptor \u03b6 (TCR\u03b6): fluorescence imaging of dynamic changes upon cellular stimulation. J. Cell Biol. 143, 613\u2013624 (1998).","journal-title":"J. Cell Biol."},{"key":"BFnri1245_CR47","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1084\/jem.186.10.1713","volume":"186","author":"J Sloan-Lancaster","year":"1997","unstructured":"Sloan-Lancaster, J. et al. Regulation of ZAP-70 intracellular localization: visualization with the green fluorescent protein. J. Exp. Med. 186, 1713\u20131724 (1997).","journal-title":"J. Exp. Med."},{"key":"BFnri1245_CR48","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1083\/jcb.200203043","volume":"158","author":"SC Bunnell","year":"2002","unstructured":"Bunnell, S. C. et al. T cell receptor ligation induces the formation of dynamically regulated signaling assemblies. J. Cell Biol. 158, 1263\u20131275 (2002).","journal-title":"J. Cell Biol."},{"key":"BFnri1245_CR49","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1016\/S1074-7613(02)00481-8","volume":"17","author":"LI Ehrlich","year":"2002","unstructured":"Ehrlich, L. I., Ebert, P. J., Krummel, M. F., Weiss, A. & Davis, M. M. Dynamics of p56lck translocation to the T cell immunological synapse following agonist and antagonist stimulation. Immunity 17, 809\u2013822 (2002).","journal-title":"Immunity"},{"key":"BFnri1245_CR50","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1126\/science.1067710","volume":"295","author":"KH Lee","year":"2002","unstructured":"Lee, K. H. et al. T cell receptor signaling precedes immuno- logical synapse formation. Science 295, 1539\u20131542 (2002). This paper and reference 52 provide a relation between TCR signalling and the formation of the immune synapse.","journal-title":"Science"},{"key":"BFnri1245_CR51","doi-asserted-by":"crossref","unstructured":"Lee, K. H. et al. The immunological synapse balances TCR signaling and degradation. Science Sept (2003) doi: 10.1126\/science.1086507.","DOI":"10.1126\/science.1086507"},{"key":"BFnri1245_CR52","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1038\/ni951","volume":"4","author":"JB Huppa","year":"2003","unstructured":"Huppa, J. B., Gleimer, M., Sumen, C. & Davis, M. M. Continuous T cell receptor signaling required for synapse maintenance and full effector potential. Nature Immunol. 4, 749\u2013755 (2003).","journal-title":"Nature Immunol."},{"key":"BFnri1245_CR53","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1084\/jem.20020158","volume":"196","author":"AG Schrum","year":"2002","unstructured":"Schrum, A. G. & Turka, L. A. The proliferative capacity of individual naive CD4+ T cells is amplified by prolonged T cell antigen receptor triggering. J. Exp. Med. 196, 793\u2013803 (2002).","journal-title":"J. Exp. Med."},{"key":"BFnri1245_CR54","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.4049\/jimmunol.171.3.1128","volume":"171","author":"M Faroudi","year":"2003","unstructured":"Faroudi, M., Zaru, R., Paulet, P., Muller, S. & Valitutti, S. Cutting edge: T lymphocyte activation by repeated immunological synapse formation and intermittent signaling. J. Immunol. 171, 1128\u20131132 (2003).","journal-title":"J. Immunol."},{"key":"BFnri1245_CR55","doi-asserted-by":"publisher","first-page":"4278","DOI":"10.4049\/jimmunol.166.7.4278","volume":"166","author":"P Reichert","year":"2001","unstructured":"Reichert, P., Reinhardt, R. L., Ingulli, E. & Jenkins, M. K. Cutting edge: in vivo identification of TCR redistribution and polarized IL-2 production by naive CD4 T cells. J. Immunol. 166, 4278\u20134281 (2001).","journal-title":"J. Immunol."},{"key":"BFnri1245_CR56","doi-asserted-by":"publisher","first-page":"1873","DOI":"10.1126\/science.1071065","volume":"296","author":"S Stoll","year":"2002","unstructured":"Stoll, S., Delon, J., Brotz, T. M. & Germain, R. N. Dynamic imaging of T cell\u2013dendritic cell interactions in lymph nodes. Science 296, 1873\u20131876 (2002).","journal-title":"Science"},{"key":"BFnri1245_CR57","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/S1074-7613(00)00032-7","volume":"13","author":"M Gunzer","year":"2000","unstructured":"Gunzer, M. et al. Antigen presentation in extracellular matrix: interactions of T cells with dendritic cells are dynamic, short lived, and sequential. Immunity 13, 323\u2013332 (2000).","journal-title":"Immunity"},{"key":"BFnri1245_CR58","doi-asserted-by":"publisher","first-page":"1869","DOI":"10.1126\/science.1070051","volume":"296","author":"MJ Miller","year":"2002","unstructured":"Miller, M. J., Wei, S. H., Parker, I. & Cahalan, M. D. Two-photon imaging of lymphocyte motility and antigen response in intact lymph node. Science 296, 1869\u20131873 (2002). References 56, 57 and 58 are landmark imaging studies that provided the first insight into the dynamics of T-cell priming.","journal-title":"Science"},{"key":"BFnri1245_CR59","doi-asserted-by":"publisher","first-page":"2604","DOI":"10.1073\/pnas.2628040100","volume":"100","author":"MJ Miller","year":"2003","unstructured":"Miller, M. J., Wei, S. H., Cahalan, M. D. & Parker, I. Autonomous T cell trafficking examined in vivo with intravital two-photon microscopy. Proc. Natl Acad. Sci. USA 100, 2604\u20132609 (2003).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnri1245_CR60","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/S1074-7613(00)80461-6","volume":"8","author":"G Iezzi","year":"1998","unstructured":"Iezzi, G., Karjalainen, K. & Lanzavecchia, A. The duration of antigenic stimulation determines the fate of naive and effector T cells. Immunity 8, 89\u201395 (1998).","journal-title":"Immunity"},{"key":"BFnri1245_CR61","doi-asserted-by":"publisher","first-page":"2263","DOI":"10.1126\/science.282.5397.2263","volume":"282","author":"KM Lee","year":"1998","unstructured":"Lee, K. M. et al. Molecular basis of T cell inactivation by CTLA4. Science 282, 2263\u20132266 (1998).","journal-title":"Science"},{"key":"BFnri1245_CR62","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1038\/ni0702-611","volume":"3","author":"JG Egen","year":"2002","unstructured":"Egen, J. G., Kuhns, M. S. & Allison, J. P. CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nature Immunol. 3, 611\u2013618 (2002).","journal-title":"Nature Immunol."},{"key":"BFnri1245_CR63","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/S1074-7613(01)00259-X","volume":"16","author":"JG Egen","year":"2002","unstructured":"Egen, J. G. & Allison, J. P. Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is regulated by TCR signal strength. Immunity 16, 23\u201335 (2002).","journal-title":"Immunity"},{"key":"BFnri1245_CR64","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1146\/annurev.immunol.18.1.275","volume":"18","author":"JT Harty","year":"2000","unstructured":"Harty, J. T., Tvinnereim, A. R. & White, D. W. CD8+ T cell effector mechanisms in resistance to infection. Annu. Rev. Immunol. 18, 275\u2013308 (2000).","journal-title":"Annu. Rev. Immunol."},{"key":"BFnri1245_CR65","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/S1074-7613(01)00234-5","volume":"15","author":"JC Stinchcombe","year":"2001","unstructured":"Stinchcombe, J. C., Bossi, G., Booth, S. & Griffiths, G. M. The immunological synapse of CTL contains a secretory domain and membrane bridges. Immunity 15, 751\u2013761 (2001). A study that provides detailed insight into the architecture of the cytotoxic T lymphocyte\u2013target cell synapse.","journal-title":"Immunity"},{"key":"BFnri1245_CR66","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1038\/ni843","volume":"3","author":"DB McGavern","year":"2002","unstructured":"McGavern, D. B., Christen, U. & Oldstone, M. B. Molecular anatomy of antigen-specific CD8+ T cell engagement and synapse formation in vivo. Nature Immunol. 3, 918\u2013925 (2002).","journal-title":"Nature Immunol."},{"key":"BFnri1245_CR67","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/S1074-7613(02)00262-5","volume":"16","author":"JR Kuhn","year":"2002","unstructured":"Kuhn, J.R. & Poenie, M. Dynamic polarization of the microtubule cytoskeleton during CTL-mediated killing. Immunity 16, 111\u2013121 (2002).","journal-title":"Immunity"},{"key":"BFnri1245_CR68","doi-asserted-by":"publisher","first-page":"1876","DOI":"10.1126\/science.1070945","volume":"296","author":"P Bousso","year":"2002","unstructured":"Bousso, P., Bhakta, N. R., Lewis, R. S. & Robey, E. Dynamics of thymocyte\u2013stromal cell interactions visualized by two-photon microscopy. Science 296, 1876\u20131880 (2002). The first in vivo imaging study on thymic selection.","journal-title":"Science"},{"key":"BFnri1245_CR69","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/S1074-7613(02)00299-6","volume":"16","author":"LI Richie","year":"2002","unstructured":"Richie, L. I. et al. Imaging synapse formation during thymocyte selection: inability of CD3\u03b6 to form a stable central accumulation during negative selection. Immunity 16, 595\u2013606 (2002).","journal-title":"Immunity"},{"key":"BFnri1245_CR70","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/S1074-7613(02)00326-6","volume":"16","author":"E Hailman","year":"2002","unstructured":"Hailman, E., Burack, W. R., Shaw, A. S., Dustin, M. L. & Allen, P. M. Immature CD4+CD8+ thymocytes form a multifocal immunological synapse with sustained tyrosine phosphorylation. Immunity 16, 839\u2013848 (2002).","journal-title":"Immunity"},{"key":"BFnri1245_CR71","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/32588","volume":"392","author":"J Banchereau","year":"1998","unstructured":"Banchereau, J. & Steinman, R. M. Dendritic cells and the control of immunity. Nature 392, 245\u2013252 (1998).","journal-title":"Nature"},{"key":"BFnri1245_CR72","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1126\/science.1071059","volume":"296","author":"P Matzinger","year":"2002","unstructured":"Matzinger, P. The danger model: a renewed sense of self. Science 296, 301\u2013305 (2002).","journal-title":"Science"},{"key":"BFnri1245_CR73","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1126\/science.1080106","volume":"299","author":"ES Trombetta","year":"2003","unstructured":"Trombetta, E. S., Ebersold, M., Garrett, W., Pypaert, M. & Mellman, I. Activation of lysosomal function during dendritic cell maturation. Science 299, 1400\u20131403 (2003).","journal-title":"Science"},{"key":"BFnri1245_CR74","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1038\/nature01006","volume":"418","author":"A Chow","year":"2002","unstructured":"Chow, A., Toomre, D., Garrett, W. & Mellman, I. Dendritic cell maturation triggers retrograde MHC class II transport from lysosomes to the plasma membrane. Nature 418, 988\u2013994 (2002).","journal-title":"Nature"},{"key":"BFnri1245_CR75","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1038\/nature01004","volume":"418","author":"M Boes","year":"2002","unstructured":"Boes, M. et al. T-cell engagement of dendritic cells rapidly rearranges MHC class II transport. Nature 418, 983\u2013988 (2002). Together with reference 74, these studies show that T-cell engagement of dendritic cells (DCs) triggers targeted transport of MHC class II molecules from lysosomes to the immune synapse. This means that signalling occurs in DCs in response to interactions with antigen-specific T cells.","journal-title":"Nature"},{"key":"BFnri1245_CR76","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.1126\/science.291.5508.1537","volume":"291","author":"P Lang","year":"2001","unstructured":"Lang, P. et al. TCR-induced transmembrane signaling by peptide\/MHC class II via associated Ig-\u03b1\/\u03b2 dimers. Science 291, 1537\u20131540 (2001).","journal-title":"Science"},{"key":"BFnri1245_CR77","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1126\/science.1084238","volume":"300","author":"D McDonald","year":"2003","unstructured":"McDonald, D. et al. Recruitment of HIV and its receptors to dendritic cell\u2013T cell junctions. Science 300, 1295\u20131297 (2003).","journal-title":"Science"},{"key":"BFnri1245_CR78","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/S0092-8674(00)80694-7","volume":"100","author":"TB Geijtenbeek","year":"2000","unstructured":"Geijtenbeek, T. B. et al. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell 100, 587\u2013597 (2000).","journal-title":"Cell"},{"key":"BFnri1245_CR79","doi-asserted-by":"publisher","first-page":"R289","DOI":"10.1016\/S0960-9822(01)00165-8","volume":"11","author":"SJ Davis","year":"2001","unstructured":"Davis, S. J. & van der Merwe, P. A. The immunological synapse: required for T cell receptor signalling or directing T cell effector function? Curr. Biol. 11, R289\u2013R291 (2001).","journal-title":"Curr. Biol."}],"container-title":["Nature Reviews Immunology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nri1245.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nri1245","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nri1245.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T04:04:56Z","timestamp":1684469096000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nri1245"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,12]]},"references-count":79,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2003,12]]}},"alternative-id":["BFnri1245"],"URL":"https:\/\/doi.org\/10.1038\/nri1245","relation":{},"ISSN":["1474-1733","1474-1741"],"issn-type":[{"value":"1474-1733","type":"print"},{"value":"1474-1741","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,12]]}}}