HLA-DO IS A LYSOSOMAL RESIDENT WHICH REQUIRES ASSOCIATION WITH HLA-DMFOR EFFICIENT INTRACELLULAR-TRANSPORT

The murine MHC class II molecule H2-O is expressed in B-cells and in t hymic epithelium but the human equivalent, HLA-DO (DO), has not been d etected, though the corresponding genes, HLA-DNA and HLA-DOB, are well known, Here we show DO to be a lysosomal resident in B-cells, Surpris ingly, DO forms stable complexes with HLA-DM (DM), another lysosomal c lass II-like molecule which is important for class II-restricted antig en presentation, Association with DM is necessary for efficient exit o f DO from the endoplasmic reticulum (ER) and thus for accumulation in lysosomes, The association is evolutionarily conserved and in mice lac king H2-M, the mouse equivalent of DM, the amount of intracellular H2- O is decreased and only minor amounts of H2-O appear to leave the ER, The DO-DM complexes survive in the lysosomal system suggesting that DO and DM functions may be intertwined.