HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 25, 23820-23828, June 24, 2005

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 280/25/23820    most recent M500654200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cebecauer, M. Articles by Luescher, I. F. Search for Related Content PubMed PubMed Citation Articles by Cebecauer, M. Articles by Luescher, I. F. Social Bookmarking                      What's this?

CD8+ Cytotoxic T Lymphocyte Activation by Soluble Major Histocompatibility Complex-Peptide Dimers^*

Marek Cebecauer, Philippe Guillaume, Silke Mark, Olivier Michielin, Nicole Boucheron, Michael Bezard, Bruno H. Meyer, Jean-Manuel Segura, Horst Vogel, and Immanuel F. Luescher¶

From the Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland and The Laboratory of Physical Chemistry of Polymers and Membranes, Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology, 1015 Lausanne, Switzerland

CD8+ cytotoxic T lymphocyte (CTL) can recognize and kill target cells that express only a few cognate major histocompatibility complex class I-peptide (pMHC) complexes. To better understand the molecular basis of this sensitive recognition process, we studied dimeric pMHC complexes containing linkers of different lengths. Although dimers containing short (10–30-Å) linkers efficiently bound to and triggered intracellular calcium mobilization and phosphorylation in cloned CTL, dimers containing long linkers (80 Å) did not. Based on this and on fluorescence resonance energy transfer experiments, we describe a dimeric binding mode in which two T cell receptors engage in an anti-parallel fashion two pMHC complexes facing each other with their constant domains. This binding mode allows integration of diverse low affinity interactions, which increases the overall binding and, hence, the sensitivity of antigen recognition. In proof of this, we demonstrated that pMHC dimers containing one agonist and one null ligand efficiently activate CTL, corroborating the importance of endogenous pMHC complexes in antigen recognition.

Received for publication, January 18, 2005 , and in revised form, March 17, 2005.

^* This study was supported by grants from the Swiss National Foundation (31-1946.00) and the Stanley Thomas Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental movies 1–3.

^¶ To whom correspondence should be addressed: Ludwig Institute for Cancer Research, Lausanne Branch, 1066 Epalinges, Switzerland. Tel.: 41-21-692-5988; Fax: 41-21-692-59-95; E-mail: immanuel.luescher{at}isrec.unil.ch.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J.-M. Segura, P. Guillaume, S. Mark, D. Dojcinovic, A. Johannsen, G. Bosshard, G. Angelov, D. F. Legler, H. Vogel, and I. F. Luescher Increased Mobility of Major Histocompatibility Complex I-Peptide Complexes Decreases the Sensitivity of Antigen Recognition J. Biol. Chem., August 29, 2008; 283(35): 24254 - 24263. [Abstract] [Full Text] [PDF]

				D. Naeher, M. A. Daniels, B. Hausmann, P. Guillaume, I. Luescher, and E. Palmer A constant affinity threshold for T cell tolerance J. Exp. Med., October 29, 2007; 204(11): 2553 - 2559. [Abstract] [Full Text] [PDF]

				N. J. Rowbotham, A. L. Hager-Theodorides, M. Cebecauer, D. K. Shah, E. Drakopoulou, J. Dyson, S. V. Outram, and T. Crompton Activation of the Hedgehog signaling pathway in T-lineage cells inhibits TCR repertoire selection in the thymus and peripheral T-cell activation Blood, May 1, 2007; 109(9): 3757 - 3766. [Abstract] [Full Text] [PDF]

				N. Anikeeva, T. Lebedeva, A. R. Clapp, E. R. Goldman, M. L. Dustin, H. Mattoussi, and Y. Sykulev Quantum dot/peptide-MHC biosensors reveal strong CD8-dependent cooperation between self and viral antigens that augment the T cell response PNAS, November 7, 2006; 103(45): 16846 - 16851. [Abstract] [Full Text] [PDF]

				P. Guillaume, P. Baumgaertner, G. S. Angelov, D. Speiser, and I. F. Luescher Fluorescence-Activated Cell Sorting and Cloning of Bona Fide CD8+ CTL with Reversible MHC-Peptide and Antibody Fab' Conjugates J. Immunol., September 15, 2006; 177(6): 3903 - 3912. [Abstract] [Full Text] [PDF]

				G. S. Angelov, P. Guillaume, M. Cebecauer, G. Bosshard, D. Dojcinovic, P. Baumgaertner, and I. F. Luescher Soluble MHC-Peptide Complexes Containing Long Rigid Linkers Abolish CTL-Mediated Cytotoxicity J. Immunol., March 15, 2006; 176(6): 3356 - 3365. [Abstract] [Full Text] [PDF]