Journal article

Differential MHC class II synthesis and ubiquitination confers distinct antigen-presenting properties on conventional and plasmacytoid dendritic cells

Louise J Young, Nicholas S Wilson, Petra Schnorrer, Anna Proietto, Toine ten Broeke, Yohei Matsuki, Adele M Mount, Gabrielle T Belz, Meredith O'Keeffe, Mari Ohmura-Hoshino, Satoshi Ishido, Willem Stoorvogel, William R Heath, Ken Shortman, Jose A Villadangos



The importance of conventional dendritic cells (cDCs) in the processing and presentation of antigen is well established, but the contribution of plasmacytoid dendritic cells (pDCs) to these processes, and hence to T cell immunity, remains unclear. Here we showed that unlike cDCs, pDCs continued to synthesize major histocompatibility complex (MHC) class II molecules and the MHC class II ubiquitin ligase MARCH1 long after activation. Sustained MHC class II-peptide complex formation, ubiquitination and turnover rendered pDCs inefficient in the presentation of exogenous antigens but enabled pDCs to continuously present endogenous viral antigens in their activated state. As the antigen-presenting..

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Awarded by Grants-in-Aid for Scientific Research

Funding Acknowledgements

We thank E. Unanue (Washington University) and R. Gugasyan (the Walter and Eliza Hall Institute) for antibody Aw3.18; M. Jenkins (University of Minnesota Medical School) for act- mOVA mice; E. Maraskovsky (CSL) for Alexa Fluor 488 - conjugated OVA; L. Brown (University of Melbourne, Australia) for the influenza strain A/PR/8/34; P. Benaroch for sharing unpublished information and critically reading the manuscript; and D. John, F. Kupresanin and all members of the Flow Cytometry and Animal Services facilities at The Walter and Eliza Hall Institute of Medical Research for technical assistance. Supported by the National Health and Medical Research Council of Australia (G.T.B., W.R.H. and J.A.V.), the Anti-Cancer Council of Australia (J.A.V.), the Gottlieb Daimler and Karl Benz Foundation (P.S.), the Wellcome Trust (G.T.B.), the Howard Hughes Medical Institute (G.T.B. and W. R. H.), the Ministry of Education, Culture, Sports, Science and Technology of Japan (S.I.), the Japan Society for the Promotion of Science (S.I.), the University of Melbourne (L.J.Y., N.S.W. and A.M.M.) and the Leukemia and Lymphoma Society J.A.V.).