Extracellular antigen processing and presentation by immature dendritic cells

In antigen presentation to CD4(+) T cells, proteins are degraded to peptide fragments and loaded onto class II MHC molecules in a process involving th e peptide exchange factors H-2M (murine) or HLA-DM (human), In many antigen -presenting cells these processes occur in intracellular endosomal compartm ents, where peptides are generated and loaded onto class II MHC proteins fo r subsequent transport to the surface and presentation to T cells. Here, we provide evidence for an additional antigen-processing pathway in immature dendritic cells (DC), Immature DC express at the cell surface empty or pept ide-receptive class II MHC molecules, as well as H-2M or HLA-DM. Secreted D C proteases act extracellularly to process intact proteins into antigenic p eptides. Peptides produced by such activity are efficiently loaded onto cel l surface class II MHC molecules, Together these elements comprise an unusu al extracellular presentation pathway in which antigen processing and pepti de loading can occur entirely outside of the cell.