Ligand selection and trafficking for MHC I

At the cell surface, the function of major histocompatibility complex class I proteins (MHC I) is to present peptide to T cell receptors (TCRs – the receptors on the surface of T cells) and recruit cofactor CD8 (coreceptor molecule on the surface of MHC I restricted T cells which bind to the α3 domain of MHC I). Inside the cell, the function of MHC I is to select peptides for presentation (collectively forming the immunome) from a pool (collectively called the peptidome) derived mainly in the cytoplasm and delivered to the endoplasmic reticulum by TAP, the transporter associated with antigen presentation. MHC I peptide selection is assisted by cofactors in the early secretory pathway including the peptide-loading complex (PLC) in the ER, which comprises newly assembled MHC I:beta2-microglobulin (β2m), tapasin, ERp57, calreticulin and TAP; and UDP-glucose:glycoprotein glucosyltransferase (UGGT), the tapasin-related protein TAPBPR, and calreticulin in the cis-Golgi. Initial binding of peptides to MHC is not thought to be very selective: selection is achieved by subsequent ‘filtration’ or ‘refinement’ steps. The first occurs in the PLC and is assisted primarily by tapasin; the second occurs in the cis-Golgi network and is assisted primarily by TAPBPR, UGGT, and calreticulin; and the third occurs at the cell surface