title: Mechanisms of peptide repertoire selection by HLA-DM.
abstract: Recently, crystal structures of key complexes in antigen presentation have been reported. HLA-DM functions in antigen presentation by catalyzing dissociation of an invariant chain remnant from the peptide binding groove and stabilizing empty MHC class II proteins in a peptide-receptive conformation. The crystal structure of a MHC class II-HLA-DM complex explains how HLA-DM stabilizes an otherwise short-lived transition state and promotes a rapid peptide exchange process that favors the highest-affinity ligands. HLA-DO has sequence similarity with MHC class II molecules yet inhibits antigen presentation. The structure of the HLA-DO-HLA-DM complex shows that it blocks HLA-DM activity as a substrate mimic. Alterations in the efficiency of DM-mediated peptide selection may contribute to autoimmune pathologies, which will be an exciting area for future investigation.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Wouter
authors.initials: W
authors.lastname: Pos
authors.forename: Dhruv K
authors.initials: DK
authors.lastname: Sethi
authors.forename: Kai W
authors.initials: KW
authors.lastname: Wucherpfennig
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D006681:HLA-D Antigens / Q000737:chemistry* / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000276:immunology*; D006801:Humans; D010455:Peptides / Q000276:immunology; D011485:Protein Binding / Q000276:immunology
chemical_list: D006681:HLA-D Antigens; C084245:HLA-DM antigens; D000949:Histocompatibility Antigens Class II; D010455:Peptides
keywords: MHC class II molecules; antigen presentation