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Nat Immunol. 2003 Nov;4(11):1065-73. Epub 2003 Oct 19.

Control of dendritic cell cross-presentation by the major histocompatibility complex class I cytoplasmic domain.

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1
Biotechnology Laboratory, Biomedical Research Centre, and the Department of Medical Genetics, University of British Columbia, Vancouver, Canada V6T 1Z3.

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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PMID:
14566337
DOI:
10.1038/ni989
[Indexed for MEDLINE]

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