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Blood, 15 July 2005, Vol. 106, No. 2, pp. 601-608. Prepublished online as a Blood First Edition Paper on March 24, 2005; DOI 10.1182/blood-2004-12-4763. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-12-4763v1 106/2/601    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Risueño, R. M. Articles by Alarcón, B. Search for Related Content PubMed PubMed Citation Articles by Risueño, R. M. Articles by Alarcón, B. Related Collections Immunobiology Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Ligand-induced conformational change in the T-cell receptor associated with productive immune synapses Ruth M. Risueño, Diana Gil, Edgar Fernández, Francisco Sánchez-Madrid, and Balbino Alarcón From the Centro de Biología Molecular Severo Ochoa (CBMSO), Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, and Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Spain; and the Laboratory of Transplantation Immunology and Nephrology, University Hospital-Basel, Switzerland. Triggering of the T-cell receptor (TCR) can produce very different responses, depending on the nature of the major histocompatibility complex/antigen peptide (MHCp) ligand. The molecular mechanisms that permit such fine discrimination are still unknown. We show here that an epitope in the cytoplasmic tail of the TCR CD3 subunit, recognized by antibody APA1/1, is only detected when the TCR is fully activated. Exposure of the APA1/1 epitope is shown to be fast and independent of tyrosine kinase activity and that it takes place even when T cells are stimulated at 0°C. These results suggest that APA1/1 detects a conformational change in the TCR. APA1/1 staining concentrates in a restricted area of the immunologic synapse. Most important, we show that full agonist, but not partial agonist, peptides induce exposure of the APA1/1 epitope, indicating a correlation between the induction of the conformational change in the TCR and full T-cell activation. Finally, the conformational change is shown to occur in T cells that are being stimulated by antigen in vivo. Therefore, these results demonstrate that the TCR undergoes a conformational change on MHCp binding in vitro and in vivo, and they establish a molecular correlate for productive TCR engagement. (Blood. 2005;106:601-608) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Antibody catches T-cell receptor in the act Michael L. Dustin Blood 2005 106: 396. [Full Text] [PDF] This article has been cited by other articles: L. M. DeFord-Watts, T. C. Tassin, A. M. Becker, J. J. Medeiros, J. P. Albanesi, P. E. Love, C. Wulfing, and N. S. C. van Oers The Cytoplasmic Tail of the T Cell Receptor CD3 {epsilon} Subunit Contains a Phospholipid-Binding Motif that Regulates T Cell Functions J. Immunol., July 15, 2009; 183(2): 1055 - 1064. [Abstract] [Full Text] [PDF] B. Acosta-Iborra, A. Elorza, I. M. Olazabal, N. B. Martin-Cofreces, S. Martin-Puig, M. Miro, M. J. Calzada, J. Aragones, F. Sanchez-Madrid, and M. O. 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