Mechanism of peptide processing and loading on MHC class II molecules
STEP 1: MHC MOLECULE ASSEMBLY IN THE ER The MHC class II subunits α and β chains both have signal sequences that facilitate co-translational import into the endoplasmic reticulum (ER). To prevent loading of MHC class II molecules with peptides generated for class I loading, the MHC class II molecules associate with the invariant chain in the ER.
Mechanism of peptide processing and loading on MHC class II molecules
STEP 2: CLIP PRODUCTION The MHC class II bound to the invariant chain travels through the secretory pathway to a late endosome, where the invariant chain is digested and the peptide CLIP remains associated with MHC class II.
Mechanism of peptide processing and loading on MHC class II molecules
STEP 3: PHAGOCYTOSIS AND FUSION WITH THE MHC COMPARTMENT Phagocytic cells internalize and digest material through phagocytosis and the phagolysosome fuses with the MHC class II vesicle.
Mechanism of peptide processing and loading on MHC class II molecules
STEP 4: PEPTIDE LOADING A vesicle containing HLA-DM fuses with the MHC class II vesicle and facilitates loading of peptides generated during phagocytosis in place of CLIP on MHC class II molecules. Loaded MHC class II molecules can then travel to the plasma membrane to present antigen to CD4 T cells.