Amphisomal route of MHC class I cross-presentation in bacteria-infected dendritic cells.

Dendritic cells (DCs) are among the first professional APCs encountered by the obligate intracellular bacterium Chlamydia during infection. Using an established mouse bone marrow-derived DC line, we show that DCs control chlamydial infection in multiple small inclusions characterized by restricted bacterial growth, impaired cytosolic export of the virulence factor chlamydial protease-like activity factor, and interaction with guanylate-binding protein 1, a host cell factor involved in the initiation of autophagy. During maturation of infected DCs, chlamydial inclusions disintegrate, likely because they lack chlamydial protease-like activity factor-mediated protection.

Post-endoplasmic reticulum rescue of unstable MHC class I requires proprotein convertase PC7.

The function of the peptide-loading complex (PLC) is to facilitate loading of MHC class I (MHC I) molecules with antigenic peptides in the endoplasmic reticulum and to drive the selection of these ligands toward a set of high-affinity binders. When the PLC fails to perform properly, as frequently observed in virus-infected or tumor cells, structurally unstable MHC I peptide complexes are generated, which are prone to disintegrate instead of presenting Ags to cytotoxic T cells. In this study we show that a second quality control checkpoint dependent on the serine protease proprotein convertase 7 (PC7) can rescue unstable MHC I, whereas the related convertase furin is completely dispensable.