Nature Immunology4, 1065 - 1073 (2003)
Published online: 19 October 2003; | doi:10.1038/ni989
Control of dendritic cell cross-presentation by the major histocompatibility complex class I cytoplasmic domain
Gregory Lizée1, 3, Genc Basha1, 3, Jacqueline Tiong1, Jean-Pierre Julien2, Meimei Tian1, Kaan E Biron1
& Wilfred A Jefferies1
1
Biotechnology Laboratory, Biomedical Research Centre, and the Departments of Medical Genetics, Microbiology and Immunology, and Zoology, University of British Columbia, Vancouver, Canada V6T 1Z3.
2
Centre for Research in Neurosciences, McGill University, Montreal, Canada H3G 1A4.
3
G.L. and G.B. contributed equally to this work.
Correspondence should be addressed to Wilfred A Jefferies wilf@brc.ubc.ca
Dendritic cells (DCs) can present extracellularly derived antigens in the context of major histocompatibility complex (MHC) class I molecules, a process called cross-presentation. Although recognized to be important for priming of T cell responses to many viral, bacterial and tumor antigens, the mechanistic details of this alternative antigen-presentation pathway are poorly understood. We demonstrate here the existence of an endolysosomal compartment in DCs where exogenously derived peptides can be acquired for presentation to T cells, and show that the MHC class I cytoplasmic domain contains a tyrosine-based targeting signal required for routing MHC class I molecules through these compartments. We also report that transgenic mice expressing H-2Kb with a tyrosine mutation mount inferior H-2Kb-restricted cytotoxic T lymphocyte responses against two immunodominant viral epitopes, providing evidence of a crucial function for cross-priming in antiviral immunity.
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