Viral antigens obstruct MHC class I antigen processing and presentation via three major pathways:
Inhibiting MHC class I expression on cells
Blocking peptide movement on MHC class I molecules
and Inhibiting peptide generation in host cells
For the reasons outlined by Røder et al. (2008) the MHC class II pathway must be utilised. Both are outlined below.
Endogenous, peptides adhere to MHC class I molecules. This occurs when an antigen enters a cell. Proteosomes degrade the cytosolic proteins into peptide fragments which are then transported by TAP (Transporters associated with Antigen Processing) to the ER (Endoplasmic Reticulum) to enable interaction with MHC molecules. Peptides are then loaded onto the molecule and the newly formed MHC class I peptide complex is released from the chaperones before moving to the cell surface via the golgi apparatus. Upon arrival, it integrates into the membrane and can then be presented and recognised by the CD8+ T-cells.
Exogenous peptides originate from outside a host cell and are internalised via an endosome before fusing with a lysosome to form an endolysosome. Here, the pathogens are digested by proteolytic lysosomal enzymes into small peptide fragments. In the rough ER, the alpha and beta chains of the MHC II molecules associate with a third protein ‘invariant’ chain. This binds to the groove of the MHC II molecule and serves to stop self peptides in the rough ER from binding to the MHC molecule. These MHC II invariant chain complexes are transported from the ER to the golgi. Now, the invariant chain is mostly digested and only a small fragment known as CLIP (Class II associated Invariant chain Polypeptide) remains bound to the MHC II molecule. The vesicle containing the MHC II-CLIP complex fuses with the vesicle containing peptide fragments of internalised antigen. The peptide fragments displace the CLIP and bind to the MHC II molecule before being transported to the cell surface and presented to CD4+ T cells.
In certain instances, cross-presentation can occur. This encompasses the process whereby exogenous antigens are presented by MHC class I molecules. MHC class II molecules may also present endogenous antigens after they have been degraded via autophagy. (British Society for Immunology 2010, para. 2)