Assembly, Peptide Loading, and Transport of MHC Class I Molecules in a Calnexin-negative Cell Line

Abstract

The class I major histocompatibility complex (MHC) molecule is a heterotrimeric complex consist-ing of a 44- to 49-kD transmembrane heavy chain, a 12-kD 1~2-microglobulin (132m) molecule, and a short pep-tide generally of 8-10 amino acid residues. The as-sembly of this complex occurs in the endoplasmic reticulum (ER) and involves the association of the heavy chain with 132m followed by the loading of the heavy chain-132m dimers with peptides (for review, see Germain and Margulies 1993). A majority of class-I-associated peptides are generated by the proteolysis of cytosolic proteins, probably by the multicatalytic proteasome complex (Goldberg and Rock 1992), and are then translocated across the ER membrane via the transporters associated with antigen processing (TAP;