GENERATION, TRANSLOCATION, AND PRESENTATION OF MHC CLASS I-RESTRICTEDPEPTIDES

The T lymphocytes of the vertebrate immune system look for changes tha t 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 multicata lytic protease, the proteasome. These peptides are translocated from t he cytosol into the endoplasmic reticulum by a dedicated peptide trans porter, the transporter associated with antigen presentation (TAP). TA P consists of two subunits, and translocates peptides that are approxi mately 8-12 residues in length. The COOH terminal residue of the pepti de is a major determinant in the specificity of translocation. Followi ng 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 trans ported to their final destination, the cell surface.