HLA-DM and HLA-DO, key regulators of MHC-II processing and presentation.
Peptide loading of class II MHC molecules in endosomal compartments is regulated by HLA-DM. HLA-DO modulates HLA-DM function, with consequences for the spectrum of MHC-bound epitopes presented at the cell surface for interaction with T cells. Here, we summarize and discuss recent progress in investigating the molecular mechanisms of action of HLA-DM and HLA-DO and in understanding their roles in immune responses. Key findings are the long-awaited structures of HLA-DM in complex with its class II substrate and with HLA-DO, and observation of a novel phenotype--autoimmunity combined with immunodeficiency--in mice lacking HLA-DO. We also highlight several areas where gaps persist in our knowledge about this pair of proteins and their molecular biology and immunobiology.
Department of Pediatrics, Program in Immunology, Stanford University, Stanford, CA 94305, United States.
Elizabeth D
ED
Mellins
Department of Pathology, Immunology and Microbiology Program, University of Massachusetts Medical School, Worcester, MA 01655, United States. Electronic address: lawrence.stern@umassmed.edu.
Lawrence J
LJ
Stern
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D018360:Crystallography, X-Ray; D006681:HLA-D Antigens / Q000737:chemistry / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000502:physiology; D011485:Protein Binding / Q000276:immunology; D015202:Protein Engineering / Q000379:methods; D040681:Structural Homology, Protein
C489628:H-2M antigen, mouse; C416186:H-2O antigen; D006681:HLA-D Antigens; C084245:HLA-DM antigens; C046148:HLA-DO antigens; D000949:Histocompatibility Antigens Class II; D010455:Peptides