Control of dendritic cell cross-presentation by the major histocompatibility complex class I cytoplasmic domain |
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Authors: | Lizée Gregory Basha Genc Tiong Jacqueline Julien Jean-Pierre Tian Meimei Biron Kaan E Jefferies Wilfred A |
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Affiliation: | Biotechnology Laboratory, Biomedical Research Centre, and the Department of Medical Genetics, University of British Columbia, Vancouver, Canada V6T 1Z3. |
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Abstract: | 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-2K(b) with a tyrosine mutation mount inferior H-2K(b)-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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