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J. Biol. Chem., Vol. 280, Issue 20, 19656-19664, May 20, 2005

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AP2 Clathrin Adaptor Complex, but Not AP1, Controls the Access of the Major Histocompatibility Complex (MHC) Class II to Endosomes^*

Marc Dugast, Hélène Toussaint¶, Christelle Dousset, and Philippe Benaroch||

From the INSERM U520 Institut Curie, Section de Recherche, 75005 Paris, France

Newly synthesized MHC II - and -chains associated with the invariant chain chaperone (Ii) enter the endocytic pathway for Ii degradation and loading with peptides before transport to the cell surface. It is unclear how Ii complexes are sorted from the Golgi apparatus and directed to endosomes. However, indirect evidence tends to support direct transport involving the AP1 clathrin adaptor complex. Surprisingly, we show here that knocking down the production of AP1 by RNA interference did not affect the trafficking of Ii complexes. In contrast, AP2 depletion led to a large increase in surface levels of Ii complexes, inhibited their rapid internalization, and strongly delayed the appearance of mature MHC II in intracellular compartments. Thus, in the cell systems studied here, rapid internalization of Ii complexes via an AP2-dependent pathway represents a key step for MHC II delivery to endosomes and lysosomes.

Received for publication, February 4, 2005 , and in revised form, February 28, 2005.

^* This work was supported by grants from the SIDACTION and Agence Nationale de Recherche sur le SIDA (ANRS). 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 Supplementary Materials.

Both authors contributed equally to this work.

Recipient of a fellowship from SIDACTION.

^¶ Recipient of a fellowship from INSERM-region.

^|| To whom correspondence should be addressed: Institut Curie INSERM U520, 26 rue d'Ulm, 75248 Paris Cedex 05, France. Tel.: 33-1-4234-6432; Fax: 33-1-4234-6438; E-mail: benaroch{at}curie.fr.

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