Early events in the assembly of MHC class I antigens

The MHC class I heavy chain and beta 2-microglobulin are cell surface proteins, and are synthesized on membrane bound ribosomes. They are co-translationally inserted into the endoplasmic reticulum (ER) membrane and assemble with antigenic peptides in the lumen of this compartment. These peptides are believed to be generated in the cytosol, and must be protected from degradation prior to translocation across the ER membrane. Putative peptide transporters (TAP1 and 2) belonging to the ABC transporter family of proteins, have been suggested to function in this process, and have been shown to be essential for MHC class I antigen assembly. The finding that peptides were translocated across the ER membrane in microsomes prepared from cells lacking the TAP genes has challenged this view. In this review we discuss the different events leading to correct assembly of MHC class I antigens. We suggest the TAP molecules to be part of a complex, which function to select peptides, protect them from degradation, and facilitate their translocation by targeting them to the ER membrane.