Plays a critical role in catalyzing the release of class II- associated invariant chain peptide (CLIP) from newly synthesized MHC class II molecules and freeing the peptide binding site for acquisition of antigenic peptides. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. {ECO:0000269|PubMed:16547258, ECO:0000269|PubMed:23260142, ECO:0000269|PubMed:8849454, ECO:0000269|PubMed:9768757}. This is the function of ENSG00000204257 (HLA-DMA, major histocompatibility complex, class II, DM alpha).