Functional HLA-DM on the surface of B cells and immature dendritic cells

HLA-DM (DM) plays a critical role in antigen presentation through major his tocompatibility complex (MHC) class II molecules. DM functions as a molecul ar chaperone by keeping class II molecules competent for antigenic peptide loading and serves as an editor by favoring presentation of high-stability peptides. Until now, DM has been thought to exert these activities only in late endosomal/lysosomal compartments of antigen-presenting cells. Here we show that a subset of DM resides at the cell surface of B cells and immatur e dendritic cells. Surface DM engages in complexes with putatively empty cl ass II molecules and controls presentation of those antigens that rely on l oading on the cell surface or in early endosomal recycling compartments. Fo r example, epitopes derived from myelin basic protein that are implicated i n the autoimmune disease multiple sclerosis are down-modulated by DM, but a re presented in the absence of DM. Thus, this novel concept of functional D M on the surface may be relevant to both protective immune responses and au toimmunity.