Meta-Biol

• Pathways

MHC class I heterodimers are only stable in peptide bound form and only as a trimer (with bound peptide) present on the cell surface. Class I MHC molecules prefer nonapeptides, and less frequently use octa- or deca-peptides. The peptide binding groove in MHC class I molecules is formed by the intimate association of the alpha1 and alpha2 domains of the heavy chain. Structural studies have revealed that the alpha1:alpha2 domains form a single peptide binding groove consisting of 2 parallel helices on a floor of 8 beta-strands. Hydrogen bonding networks are established in the binding groove with the antigenic peptide main chain and terminal atoms that enable largely sequence independent ligation. Upon peptide binding the class I MHC molecule releases from the peptide loading complex (PLC) and clusters at ER exit sites and is finally exported to the cell surface.
MHC I molecules bound to low-affinity peptides are not transferred to the cell surface and are instead cycled back to ER. They can proceed to the cell surface only when they become bound to high-affinity peptide (Howe et al, 2009; Garstka et al, 2007). Calreticulin binds to these low-affinity peptide bound class I molecules and mediate the retrieval from golgi apparatus to ER and for effcient presentation of a model antigen (Howe et al, 2009).