Generation, Translocation, and Presentation of MHC Class I-Restricted Peptides

The T lymphocytes of the vertebrate immune system look for changes that take place within the organism by examining a display of peptides at the cell surface. These peptides are presented by the products of the major histocompatibility complex (MHC). MHC class I products present peptides derived by proteolysis of cytosolic proteins by the multicatalytic protease, the proteasome. These peptides are translocated from the cytosol into the endoplasmic reticulum by a dedicated peptide transporter, the transporter associated with antigen presentation (TAP). TAP consists of two subunits, and translocates peptides that are approximately 8-12 residues in length. The COOH terminal residue of the peptide is a major determinant in the specificity of translocation. Following translocation, peptides bind to MHC class I molecules, which depend on the peptide ligand as well as on interactions with chaperonins for proper folding. These complexes then egress from the ER and are transported to their final destination, the cell surface.