Cross-presentation of epitopes on virus-like particles via the MHC I receptor recycling pathway

Immunol Cell Biol. 2011 Aug;89(6):681-8. doi: 10.1038/icb.2010.161. Epub 2011 Jan 11.


Effective vaccines and immunotherapies against cancer require professional antigen-presenting cells to cross-present exogenous antigen to initiate cytotoxic T-cell responses to destroy tumors. Virus-like particles (VLPs), containing tumor antigens, which can immunize against cancers, are cross-presented by dendritic cell (DC) but the mechanism by which this occurs is not fully understood. Here, we used VLPs, derived from rabbit hemorrhagic disease virus (RHDV) with both murine and human DCs, to elucidate these pathways. We have employed inhibitors to demonstrate that these VLPs are taken up by clathrin-dependent macropinocytosis and phagocytosis before being degraded in acidic lysosomal compartments. VLP-derived peptides are loaded onto major histocompatibility complex I that have been recycled from the cell surface. Antigen-coupled VLPs and murine ovalbumin-specific and human melanoma-associated antigen recognized by T cells (MART-1)-specific CD8(+) T cells were used to demonstrate cross-presentation via this alternate, receptor recycling pathway, which operated independently of the proteasome and the transporter-associated with antigen presentation. Finally, we found that cross-presentation of VLPs in vivo was not confined to CD8α(+) DC subsets. These data define the cross-presentation pathway for RHDV VLPs and may lead to improved cancer immunotherapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / immunology
  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Antigen Presentation / immunology*
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • Bone Marrow Cells / immunology
  • Cells, Cultured
  • Coculture Techniques
  • Cross-Priming / immunology*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Endocytosis / immunology
  • Epitopes / immunology*
  • Female
  • Hemorrhagic Disease Virus, Rabbit / immunology
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Phagocytosis / immunology
  • Pinocytosis / immunology
  • Proteome / immunology
  • Rabbits
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism
  • Spleen / immunology
  • T-Lymphocytes, Cytotoxic / immunology
  • Vaccines, Virus-Like Particle / immunology*


  • ATP-Binding Cassette Transporters
  • Epitopes
  • Histocompatibility Antigens Class I
  • Proteome
  • Receptors, Cell Surface
  • Vaccines, Virus-Like Particle
  • transporter associated with antigen processing (TAP)