The quality control of MHC class I antigen presentation

Major histocompatibility complex (MHC) class I molecules present antigenic peptides to CD8+ T cells. The peptides are generated by proteasomes in the cytosol, then translocated across the membrane of the endoplasmic reticulum (ER) by the transporter associated with antigen processing (TAP). Only properly assembled class I molecules loaded with high affinity peptides reach the cell surface. The maturation process is performed in a sequential mode where the chaperones BiP and calnexin sequentially control the folding of the MHC class I. Dimerised MHC class I then associate with the loading complex (paper I). An essential component of the loading complex is the trimeric complex consisting of TAP1, TAP2, and tapasin as shown in paper II. Due to its ability to interact with TAP and MHC class I, tapasin is a central component in the assembly of MHC class I. Efficient peptide binding by TAP prior to translocation across the ER membrane requires the presence of tapasin (paper III). Once in the ER, the assembly of tapasin-associated MHC class I with peptide depends on the presence of TAP transported peptides (paper IV). The transport of stably loaded class I molecules to the cell surface goes through the secretory route. Tapasin interacts specifically with COPI vesicles, possibly allowing recycling of unstable class I molecules from the Golgi back to the ER (paper V).