Control of dendritic cell cross-presentation by the major histocompatibility complex class I cytoplasmic domain.
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.
Lizée
Gregory
G
Biotechnology Laboratory, Biomedical Research Centre, and the Department of Medical Genetics, University of British Columbia, Vancouver, Canada V6T 1Z3.
Basha
Genc
G
Tiong
Jacqueline
J
Julien
Jean-Pierre
JP
Tian
Meimei
M
Biron
Kaan E
KE
Jefferies
Wilfred A
WA
D000818:Animals; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014443:Tyrosine / Q000378:metabolism
D015395:Histocompatibility Antigens Class I; D014443:Tyrosine