The known unknowns of antigen processing and presentation

The pathways of antigen processing and presentation are well known, but how do antigens gain access to MHC molecules in dendritic cells and what is the role of autophagy, endoplasmic reticulum dislocation and Toll-like receptors in these pathways? The principal components of both MHC class I and class II antigen processing and presentation pathways are well known. In dendritic cells, these pathways are tightly regulated by Toll-like-receptor signalling and include features, such as cross-presentation, that are not seen in other cell types. However, the exact mechanisms involved in the subcellular trafficking of antigens remain poorly understood and in some cases are controversial. Recent data suggest that diverse cellular machineries, including autophagy, participate in antigen processing and presentation, although their relative contributions remain to be fully elucidated. Here, we highlight some emerging themes of antigen processing and presentation that we think merit further attention.