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Regulation of CD1a Surface Expression and Antigen Presentation by Invariant Chain and Lipid Rafts¹

Ivan Sloma^*,, Marie-Thérèse Zilber^*, Thierry Vasselon^*, Niclas Setterblad, Marco Cavallari, Lucia Mori, Gennaro De Libero, Dominique Charron^*,, Nuala Mooney^2,* and Catherine Gelin^*

^* Institut National de la Santé et de la Recherche Médicale U662, Laboratoire d’Immunologie et Histocompatibilité, and Service Commun d’Imagerie, Institut Universitaire d’Hématologie, Hôpital Saint-Louis, Paris, France; and Experimental Immunology, Department of Research, Basel University Hospital, Basel, Switzerland

In immature dendritic cells (DCs), CD1a is almost exclusively expressed at the cell surface and its membrane organization is poorly understood. In this study, we report that MHC class II, invariant chain (Ii), and CD9 molecules are coimmunoprecipitated with CD1a in immature DCs, and that CD1a/Ii colocalization is dependent on lipid raft integrity. In HeLa-CIITA cells CD1a expression leads to increased Ii trafficking to the cell surface, confirming the relevance of this association. Furthermore, silencing of Ii in DCs induces significant CD1a accumulation on the plasma membrane whereas the total CD1a expression remains similar to that of control cells. These data suggest that CD1a recycling is facilitated by the association with the Ii. The CD1a localization in lipid rafts has functional relevance as demonstrated by inhibition of CD1a-restricted presentation following raft disruption. Overall, these findings identify Ii and lipid rafts as key regulators of CD1a organization on the surface of immature DCs and of its immunological function as Ag-presenting molecule.

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.

¹ This work was supported by Institut National de la Santé et de la Recherche Médicale, Assistance Publique-Hôpitaux de Paris, TRANSNET, and Allostem Grants MRTN-CT-2001-512253 and FP6 503319, and by the Swiss National Science Foundation Grant 3100AO-109918.

² Address correspondence and reprint requests to Dr. Nuala Mooney, Institut National de la Santé et de la Recherche Médicale U662, Institut d’Hématologie, Hôpital Saint-Louis, 1 avenue Claude Vellefaux, 75010 Paris, France. E-mail address: nuala.mooney{at}univ-paris-diderot.fr

³ Abbreviations used in this paper: MHC I, MHC class I; MHC II, MHC class II; iDC, immature dendritic cell; DC, dendritic cell; CT, cholera toxin; MβCD, Mβ-cyclodextrin; Ii, invariant chain.

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