Involvement of clathrin and AP-2 in the trafficking of MHC class II molecules to antigen-processing compartments

McCormick, Peter J, Martina, José A and Bonifacino, Juan S (2005) Involvement of clathrin and AP-2 in the trafficking of MHC class II molecules to antigen-processing compartments. Proceedings of the National Academy of Sciences, 102 (22). pp. 7910-5. ISSN 0027-8424

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Abstract

Major histocompatibility complex class II (MHC-II) molecules are composed of two polymorphic chains, alpha and beta, which assemble with an invariant chain, Ii, in the endoplasmic reticulum. The assembled MHC-II complexes are transported to the Golgi complex and then to late endosomes/lysosomes, where Ii is degraded and alphabeta dimers bind peptides derived from exogenous antigens. Targeting of MHC-II molecules to these compartments is mediated by two dileucine-based signals in the cytoplasmic domain of Ii. These signals bind in vitro to two adaptor protein (AP) complexes, AP-1 and AP-2, which are components of clathrin coats involved in vesicle formation and cargo sorting. The physiological roles of these proteins in MHC-II molecule trafficking, however, remain to be addressed. Here, we report the use of RNA interference to examine the involvement of clathrin and four AP complexes (AP-1, AP-2, AP-3, and AP-4) in MHC-II molecule trafficking in vivo. We found that depletion of clathrin or AP-2 caused >10-fold increases in Ii expression on the cell surface and a concomitant decrease in Ii localization to endosomal/lysosomal vesicles. In addition, depletion of clathrin or AP-2 delayed the degradation of Ii and reduced the surface expression of peptide-loaded alphabeta dimers. In contrast, depletion of AP-1, AP-3, or AP-4 had little or no effect. These findings demonstrate that clathrin and AP-2 participate in MHC-II molecule trafficking in vivo. Because AP-2 is only associated with the plasma membrane, these results also indicate that a significant pool of MHC-II molecules traffic to the endosomal-lysosomal system by means of the cell surface.

Item Type:	Article
Uncontrolled Keywords:	adaptor protein complex 2,antigen presentation,antigens, differentiation, b-lymphocyte,cathepsin d,clathrin,flow cytometry,hela cells,histocompatibility antigens class ii,humans,immunoblotting,immunoprecipitation,lysosomes,microscopy, fluorescence,protein transport,rna interference,rna, small interfering,signal transduction
Faculty \ School:	Faculty of Science > School of Pharmacy
Depositing User:	Pure Connector
Date Deposited:	13 Jan 2014 13:52
Last Modified:	24 Oct 2022 05:57
URI:	https://ueaeprints.uea.ac.uk/id/eprint/47173
DOI:	10.1073/pnas.0502206102

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