Which of the following is NOT a step in MHC class I antigen processing?

• A. Proteasomal degradation of cytosolic proteins
• B. TAP transport of peptides into the endoplasmic reticulum
• C. Loading onto MHC II in endosomes
• D. Surface expression of peptide-MHC I complex

Answer: (C)

MHC class I antigen processing relies on endogenous proteins being degraded by the proteasome, with the resulting peptides transported into the endoplasmic reticulum by TAP. In the ER, these peptides are loaded onto newly formed MHC class I molecules with the help of chaperones and editing proteins, and the peptide-MHC I complex is then trafficked to the cell surface for presentation to CD8+ T cells. This pathway is focused in the cytosol and the ER, not in endosomes.

Loading peptides onto MHC II in endosomes is not part of this process. MHC class II molecules present exogenous antigens that are taken up by endocytosis and processed in endosomal/lysosomal compartments, with peptide loading occurring there, often involving invariant chain and HLA-DM. The step described—loading onto MHC II in endosomes—belongs to the MHC class II pathway, not to MHC class I.