Takes place in the lumen of the endoplasmic reticulum (ER).
Initial Folding
Chaperone Calnexin aids the initial folding of the class I heavy (alpha) chain.
Further Folding
Chaperone Calreticulin aids further folding and the association of beta-2 microglobulin.
Other involved proteins: ERp57 and TAPasin.
Peptide Loading Complex
The nascent class I molecule binds to the TAP transporter via TAPasin to form the peptide loading complex.
Peptide Generation
Proteasome: Large protein complex in the cytoplasm that degrades proteins in the cytosol to produce short peptides.
These short peptides are transported through the ER membrane by the TAP transporter.
Peptide Modification
ER Aminopeptidase Associated with Antigen Processing (ERAAP): Enzyme in the ER that trims the amino terminus of peptides, making them suitable for binding to MHC molecules.
Peptide Binding and Editing
Peptide Editing: Unstable or non-binding peptides are released from the MHC molecule.
High-affinity binding: A peptide binds with high affinity to form a stable complex.
Final Steps
The stable peptide-MHC complex triggers the final folding of the class I molecule.
Dissociation of the peptide loading complex occurs.
Transport to Cell Surface
The peptide-loaded MHC class I molecule exits the ER.
Transported via the Golgi apparatus to the cell surface.