Explain specifically how interferon-? produced during an infection enhances (A) antigen processing in the MHC class I pathway, and (B) antigen presentation in the MHC class II pathway
What will be an ideal response?
A. Interferon-γ causes a shift from the production of constitutive proteasomes to that of immunoproteasomes. This is accomplished through increased expression of alternative subunits (LMP2 and LMP7) that are present in the immunoproteasome. These proteasomes exhibit modified protease activities favoring the production of peptides (antigen processing) that can bind to MHC class I molecules. Specifically, cleavage after hydrophobic residues is enhanced and cleavage after acidic residues is decreased.
B. Interferon-γ increases the expression of HLA-DM but not HLA-DO. This causes a shift in the balance of these two molecules, resulting in an overall decrease in the antagonist activity of HLA-DO. If HLA-DM is more abundant, it has the ability to catalyze the release of CLIP from MHC class II molecules and facilitate the replacement of CLIP with other peptides for presentation to CD4 T cells (antigen presentation). Another way in which interferon-γ increases antigen presentation in the MHC class II pathway is by increasing the expression levels of MHC class II molecules on both professional and non-professional antigen-presenting cells.
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