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Originally published as MBC in Press, 10.1091/mbc.E05-01-0005 on May 4, 2005

Vol. 16, Issue 7, 3314-3322, July 2005

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Synaptic Clusters of MHC Class II Molecules Induced on DCs by Adhesion Molecule–mediated Initial T-Cell Scanning{boxv}

Hortensia de la Fuente * {dagger}, María Mittelbrunn * {dagger}, Lorena Sánchez-Martín {ddagger}, Miguel Vicente-Manzanares *, Amalia Lamana *, Ruggero Pardi §, Carlos Cabañas {ddagger}, and Francisco Sánchez-Madrid *

* Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain; {ddagger} Instituto de Farmacología y Toxicología, CSIC-UCM, Facultad de Medicina, Universidad Complutense, 28040 Madrid, Spain; and § Vita-Salute San Raffaele University School of Medicine, 20132 Milano, Italy

Submitted January 4, 2005; Revised March 29, 2005; Accepted April 22, 2005
Monitoring Editor: Mark Ginsberg

Initial adhesive contacts between T lymphocytes and dendritic cells (DCs) facilitate recognition of peptide-MHC complexes by the TCR. In this report, we studied the dynamic behavior of adhesion and Ag receptors on DCs during initial contacts with T-cells. Adhesion molecules LFA-1- and ICAM-1,3-GFP as well as MHC class II-GFP molecules were very rapidly concentrated at the DC contact area. Binding of ICAM-3, and ICAM-1 to a lesser extent, to LFA-1 expressed by mature but not immature DC, induced MHC-II clustering into the immune synapse. Also, ICAM-3 binding to DC induced the activation of the Vav1-Rac1 axis, a regulatory pathway involved in actin cytoskeleton reorganization, which was essential for MHC-II clustering on DCs. Our results support a model in which ICAM-mediated MHC-II clustering on DC constitutes a priming mechanism to enhance antigen presentation to T-cells.

This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E05–01–0005) on May 4, 2005.

Abbreviations used: Ag, antigen; APC, Ag presenting cell; c-SMAC, central supramolecular activation complex; DC(s), dendritic cell(s); DIC, differential interference contrast; Gp, glycophorin; IS, immune synapse; p-SMAC, peripheral supramolecular activation complex; SEB, staphylococcal enterotoxin B.

{boxv} The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

{dagger} These authors contributed equally to this work.

Address correspondence to: Francisco Sánchez-Madrid (fsanchez.hlpr{at}salud.madrid.org).




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