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

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, FcRγIIA 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.