Nature Immunology 6, 1253 - 1262 (2005)
Published online: 6 November 2005; | doi:10.1038/ni1272
Newly generated T cell receptor microclusters initiate and sustain T cell activation by recruitment of Zap70 and SLP-76Tadashi Yokosuka1, Kumiko Sakata-Sogawa2, Wakana Kobayashi1, Michio Hiroshima2, Akiko Hashimoto-Tane1, Makio Tokunaga2, 3, 4, Michael L Dustin5
& Takashi Saito11
Laboratory for Cell Signaling, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. 2
Single-Molecule Immunoimaging, RIKEN Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. 3
Structural Biology Center, National Institute of Genetics, Shizuoka 411-8540, Japan. 4
Department of Genetics, The Graduate University for Advanced Studies, Mishima, Shizuoka 411-8540, Japan. 5
Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine and Department of Pathology, New York University School of Medicine, New York, New York 10021, USA.
Correspondence should be addressed to Takashi Saito saito@rcai.riken.jp T cell receptor (TCR) activation and signaling precede immunological synapse formation and are sustained for hours after initiation. However, the precise physical sites of the initial and sustained TCR signaling are not definitively known. We report here that T cell activation was initiated and sustained in TCR-containing microclusters generated at the initial contact sites and the periphery of the mature immunological synapse. Microclusters containing TCRs, the tyrosine kinase Zap70 and the adaptor molecule SLP-76 were continuously generated at the periphery. TCR microclusters migrated toward the central supramolecular cluster, whereas Zap70 and SLP-76 dissociated from these microclusters before the microclusters coalesced with the TCR-rich central supramolecular cluster. Tyrosine phosphorylation and calcium influx were induced as microclusters formed at the initial contact sites. Inhibition of signaling prevented recruitment of Zap70 into the microclusters. These results indicated that TCR-rich microclusters initiate and sustain TCR signaling.
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