title: Folding and assembly of major histocompatibility complex class I heterodimers in the endoplasmic reticulum of intact cells precedes the binding of peptide.
abstract: Major histocompatibility complex (MHC) class I molecules are heterotrimers consisting of a polymorphic H chain, beta 2-microglobulin (beta 2m) and peptide. Peptides are thought to associate early during biosynthesis but the order of assembly of class I molecules from their component subunits in intact cells is not settled. We have studied the assembly of MHC class I molecules in intact cells with or without peptide transporters. MHC class I H chain/beta 2m heterodimers can be efficiently recovered only 4 min after translation and are preceded by a folding intermediate. Approximately 2 min after their formation, the class I heterodimers are loaded with peptides resulting in stable class I heterotrimers. In these in vivo studies, no evidence was obtained that peptide binding to the H chain preceded the association with beta 2m. In contrast, nonassembled class I H chains could be recovered immediately after translation, but this pool did not participate in the formation of class I molecules.
authors.affiliation: Tumor Immunology Program, German Cancer Research Center, Heidelberg.
authors.forename: J J
authors.initials: JJ
authors.lastname: Neefjes
authors.forename: G J
authors.initials: GJ
authors.lastname: Hämmerling
authors.forename: F
authors.initials: F
authors.lastname: Momburg
mesh_terms: D001692:Biological Transport; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005095:Exoribonucleases; D005656:Fungal Proteins / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D015395:Histocompatibility Antigens Class I; D046911:Macromolecular Substances; D010455:Peptides; D015534:Trans-Activators; D001613:beta 2-Microglobulin; D005095:Exoribonucleases