Heat shock protein magic in antigen trafficking within dendritic cells: Implications in antigen cross-presentation in immunity

Dendritic cells (DCs) take up soluble- or cell-associated antigens and digest them, delivering fragments to the MHC class I pathway to display antigenic peptides to CD8 ⁺ T cells, a process known as cross-presentation. The pathway requires that, in order to be degraded by proteosomes, the extracellular antigens must have access to the cytosol across the endosomal membranes. Although the cross-presentation phenomena was first identified in the 1970s, the molecular mechanism responsible for the trans-location is still not fully understood. In this context, we have recently found that cytosolic heat shock protein (HSP)90 translocates internalized antigen to the cytosol in DCs. Our results revealed the important role that cytosolic HSP90 plays in cross-presentation by pulling out endosomal antigen to the cytosol.