HLA-DO

Human leukocyte histocompatibility complex DO (HLA-DO) is an intracellular, dimeric non-classical Major Histocompatibility Complex (MHC) class II protein composed of α- and β-subunits which interact with HLA-DM in order to fine tune immunodominant epitope selection.^[1][2] As a non-classical MHC class II molecule, HLA-DO is a non-polymorphic accessory protein that aids in antigenic peptide chaperoning and loading, as opposed to its classical counterparts, which are polymorphic and involved in antigen presentation.^[3][4][5] Though more remains to be elucidated about the function of HLA-DO, its unique distribution in the mammalian body—namely, the exclusive expression of HLA-DO in B cells, thymic medullary epithelial cells, and dendritic cells—indicate that it may be of physiological importance and has inspired further research.^[3][6] Although HLA-DM can be found without HLA-DO, HLA-DO is only found in complex with HLA-DM and exhibits instability in the absence of HLA-DM. The evolutionary conservation of both DM and DO, further denote its biological significance and potential to confer evolutionary benefits to its host.^[6][7][8]