Principles of MHC class I-mediated antigen presentation and T cell selection

Class I molecules of the major histocompatibility complex (MHC) are expressed on the cell surface of almost all nucleated mammalian cells. Their main function is to transport and present peptides, derived from intracellularly degraded proteins, to cytotoxic T cells (CTL). They are also directly involved in the process leading to maturation and selection of a functional CD8+ T cell repertoire. MHC class I molecules consist of a highly polymorphic membrane spanning heavy chain of approximately 45 kD that is non-covalently associated with a light chain, beta 2-microglobulin (beta 2m). Class I molecules bind peptides, usually 8-11 amino acids in length. The majority of the class I-bound peptides are generated in the cytosol and are subsequently translocated into the lumen of the endoplasmic reticulum (ER) through the ATP-dependent transporter associated with antigen processing 1/2 (TAP1/2). Here, we provide an up-to-date review summarizing the most essential parts relating to MHC class I-mediated antigen processing, presentation and T cell selection. A particular emphasis is devoted to the structure of MHC class I molecule, and MHC class I-bound peptides.