Publication Type:
Journal ArticleSource:
Nat Immunol, Volume 4, Issue 11, p.1065-73 (2003)Keywords:
Animals, Cross-Priming, Dendritic Cells, Histocompatibility Antigens Class I, Lysosomes, Mice, Mice, Transgenic, Mutation, T-Lymphocytes, Cytotoxic, TyrosineAbstract:
<p>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.</p>