Peptide translocation into the ER

Abstract

Abstract A crucial step in antigen presentation by MHC class I molecules is the translocation of peptide fragments of protein antigens from the cytosol to the lumen of the endoplasmic reticulum (ER). Here, peptides are bound with high affinity by freshly assembled MHC class I H-chain/l32m heterodimers and are then intracellularly transported to the cell surface and presented by class I molecules to cog+ T cells (1, 2). An ER-located peptide pump termed TAP (Transporter associated with Antigen Presentation) has been genetically defined and demonstrated to translocate peptides from the cytosol to the lumen of the ER (3, 4). Essential to the characterization of TAP were mutant cell lines with inactivated genes for one or both of the two subunits of TAP. In the absence of TAP activity, MHC class I molecules are not loaded with peptides. This results in retention of the class I heterodimer in the ER and decreased cell surface expression of class I molecules.