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

Nat Immunol. 2003 Nov;4(11):1065-73. doi: 10.1038/ni989. Epub 2003 Oct 19.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cross-Priming / immunology*
  • Dendritic Cells / immunology*
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology*
  • Lysosomes / metabolism
  • Mice
  • Mice, Transgenic
  • Mutation
  • T-Lymphocytes, Cytotoxic / immunology
  • Tyrosine / metabolism


  • Histocompatibility Antigens Class I
  • Tyrosine