Right place, right time, right peptide: DO keeps DM focused

Peptide loading of major histocompatibility class II molecules is catalyzed in late endosomal and lysosomal compartments of cells by the catalytic action of human leukocyte antigen (HLA)-DM (H-2M in mice). In B cells, dendritic cells and thymic epithelial cells, the peptide loading of class II molecules is modified by the expression of the non-classical class II molecule, HLA-DO (H-2O in mice). Collectively, studies to date support that DO/H-2O expression inhibits the presentation of antigens acquired by cells via fluid phase endocytosis. However, in B cells, the expression of H-2O promotes the presentation of antigens internalized by the B-cell receptor. In this review, we summarize the literature pertaining to DO assembly, transport, and function, with an emphasis on the function of DO/H-2O.