biostudies-literatureNarayan KNIAID NIH HHSNIGMS NIH HHS3157-62https://www.ebi.ac.uk/biostudies/studies/S-EPMC2743474biostudies-literatureUnknown46(15)The peptide editor HLA-DM (DM) catalyzes the exchange of peptides bound to MHC class II molecules within antigen presenting cells by generating a "peptide-receptive" MHC class II conformation (MHC(receptive)) to which peptides readily bind and rapidly unbind. While recent work has uncovered the determinants of DM recognition and effector functions, the nature of MHC(receptive) and its interaction with DM remains unclear. Here, we show that DM induces but does not stabilize MHC(receptive) in the absence of peptides. We demonstrate that DM is out-competed by certain superantigens, and increasing solvent viscosity inhibits DM-induced peptide association. We suggest that DM mediates peptide exchange by interacting transiently and repeatedly with MHC class II molecules, continually generating MHC(receptive). The simultaneous presence of peptide and DM in the milieu is thus crucial for the efficient generation of specific peptide-MHC class II complexes over time.Molecular immunologyHLA-DM mediates peptide exchange by interacting transiently and repeatedly with HLA-DR1.PMC2743474R01 GM053549-06A1R01GM53549R01 AI063764-01A2R01 AI063764R01 GM053549R01AI063764Narayan KChou CLKhoruzhenko SSadegh-Nasseri SSu KWfalseHLA-DM mediates peptide exchange by interacting transiently and repeatedly with HLA-DR1.The peptide editor HLA-DM (DM) catalyzes the exchange of peptides bound to MHC class II molecules within antigen presenting cells by generating a "peptide-receptive" MHC class II conformation (MHC(receptive)) to which peptides readily bind and rapidly unbind. While recent work has uncovered the determinants of DM recognition and effector functions, the nature of MHC(receptive) and its interaction with DM remains unclear. Here, we show that DM induces but does not stabilize MHC(receptive) in the absence of peptides. We demonstrate that DM is out-competed by certain superantigens, and increasing solvent viscosity inhibits DM-induced peptide association. We suggest that DM mediates peptide exchange by interacting transiently and repeatedly with MHC class II molecules, continually generating MHC(receptive). The simultaneous presence of peptide and DM in the milieu is thus crucial for the efficient generation of specific peptide-MHC class II complexes over time.2009-01-01T00:00:00Z2009 Sep2020-10-31T09:43:19Z2019-03-27T00:24:56ZS-EPMC27434741964732010.1016/j.molimm.2009.07.001