Figure 4.

MHC class I/II pathways enhance antigen processing and presentation. There are several ways in which to improve HPV antigen expression, processing, and presentation in DCs. Of these strategies, enhancing MHC I/II expressions in DCs helps increase antigen processing and presentation. (A) For MHC class I pathways, antigen transcription can be enhanced by diacylglycerols. (B) Plasmid design (i.e., codon optimization, Kozak/leader sequences) also enhance antigen (Ag) translation. (C) Fusion to potato virus X coat protein, γ-tubulin, or ubiquitin and destabilizing mutations target Ags for proteasomal degradation. (D) Subsequent fusion to signal peptides (i.e., adenoviral E3, IP-10, BAFF) or endoplasmic reticulum (ER) chaperone proteins (i.e., GRT, Tap, C21) target endogenous Ags to be presented onto MHC class I molecules in the ER by way of tapasin. These MHC I molecules are later transported from the ER to the extracellular matrix. (E) Single-chain trimers (SCTs) are also involved in bypassing proteasomal antigen processing. (F) Alternatively, co-administering class II transactivator and histone deacetylase inhibitor can enhance MHC I/II expressions through transcription. Class 2-associated Ii chain peptide (CLIP) is a part of the invariant chain (Ii) that binds MHC class II molecules prior to full assembly of the MHC receptor. They help prevent self-peptide fragments from binding until localization of MHC class II molecules into endosomes and lysosomes takes place. (G) Fusion to lysosomal-associated membrane protein type 1 (LAMP-1) targets Ags to the endosomes and lysosomes for export to the extracellular matrix by presentation to MHC class II molecules.