Describe in chronological order the steps of the antigen-processing and antigen-presentation pathways for extracellular pathogens

Question

What will be an ideal response?

Answer 1

Extracellular pathogens are taken up by endocytosis or phagocytosis and degraded by enzymes into smaller peptide fragments inside acidified intracellular vesicles called phagolysosomes. MHC class II molecules delivered into the ER and being transported to the cell surface intersect with the phagolysosomes, where these peptides are encountered and loaded into the antigen-binding groove. To prevent MHC class II molecules from binding to peptides prematurely, invariant chain (Ii) binds to the MHC class II antigen-binding site in the ER. Ii is also involved in transporting MHC class II molecules to the phagolysosomes via the Golgi as part of the interconnected vesicle system. Ii is removed from MHC class II molecules once the phagolysosome is reached. Removal is achieved in two steps: (1) proteolysis cleaves Ii into smaller fragments, leaving a small peptide called CLIP (class II-associated invariant chain peptide) in the antigen-binding groove of the MHC class II molecule; and (2) CLIP is then released by HLA-DM catalysis. Once CLIP is removed, HLA-DM remains associated with the MHC class II molecule, enabling the now empty peptide-binding groove to sample other peptides until one binds tightly enough to cause a conformational change that releases HLA-DM. Finally, the peptide:MHC class II complex is transported to the plasma membrane.