Receptor-mediated phagocytosis elicits cross-presentation in nonprofessional antigen-presenting cells

Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3324-9. doi: 10.1073/pnas.0813305106. Epub 2009 Feb 13.

Abstract

In cross-presentation by dendritic cells (DCs), internalized proteins are retrotranslocated into the cytosol, degraded by the proteasome, and the generated antigenic peptides bind to MHC class I molecules for presentation on the cell surface. Endoplasmic reticulum (ER) contribution to phagosomal membranes is thought to provide antigen access to the ER-associated degradation (ERAD) machinery, allowing cytosolic dislocation. Because the ERAD pathway is present in all cell types and exogenous antigens encounter an ER-containing compartment during phagocytosis, we postulated that forcing phagocytosis in cell types other than DCs would render them competent for cross-presentation. Indeed, FcRgammaIIA expression endowed 293T cells with the capacity for both phagocytosis and ERAD-mediated cross-presentation of an antigen provided as an immune complex. The acquisition of this ability by nonprofessional antigen-presenting cells suggests that a function potentially available in all cell types has been adapted by DCs for presentation of exogenous antigens by MHC class I molecules.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / immunology
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / ultrastructure
  • Calnexin / immunology
  • Calnexin / metabolism
  • Cell Line
  • Cross-Priming / immunology*
  • Dendritic Cells / immunology
  • Endoplasmic Reticulum / immunology
  • Endoplasmic Reticulum / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Microscopy, Electron, Transmission
  • Microscopy, Immunoelectron
  • Phagocytosis / immunology*
  • Receptors, IgG / immunology

Substances

  • Antibodies
  • Receptors, IgG
  • Calnexin