FOLDING AND ASSEMBLY OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I HETERODIMERS IN THE ENDOPLASMIC-RETICULUM OF INTACT-CELLS PRECEDES THE BINDING OF PEPTIDE

Major histocompatibility complex (MHC) class I molecules are heterotri mers consisting of a polymorphic H chain, beta2-microglobulin (beta2m) and peptide. Peptides are thought to associate early during biosynthe sis but the order of assembly of class I molecules from their componen t subunits in intact cells is not settled. We have studied the assembl y of MHC class I molecules in intact cells with or without peptide tra nsporters. MHC class I H chain/beta2m heterodimers can be efficiently recovered only 4 min after translation and are preceded by a folding i ntermediate. Approximately 2 min after their formation, the class I he terodimers are loaded with peptides resulting in stable class I hetero trimers. In these in vivo studies, no evidence was obtained that pepti de binding to the H chain preceded the association with beta2m. In con trast, nonassembled class I H chains could be recovered immediately af ter translation, but this pool did not participate in the formation of class I molecules.