Tumor-associated antigens (TAA) can be internalized by receptors on antigen presenting cells such as dendritic cells (DC). They are processed into short peptides by a variety of proteases and then loaded onto MHC molecules for expression on the cell surface.
Classically, the presentation of extracellular-derived antigens involves MHC class II molecules and promotes CD4+ helper T cell activation and humoral immunity. The presentation of intracellular molecules (as with virus-infected cells) alternatively involves MHC class I molecules and promotes the activation of cytolytic CD8+ T cells.
In antigen cross-presentation, extracellular antigens are presented in complex with MHC class I instead of class II molecules. For cancer vaccines, DC are engineered so they present extracellularly-derived TAA with MHC class I molecules to generate cytolytic activity directed at the tumor cells. In vacuolar cross-presentation, antigen processing and loading onto MHC-I takes place in endocytic compartments. In cytosolic cross-presentation, antigens are processed by cytosolic proteasomes before loading onto MHC-I. Cross-presentation by dendritic cells is enhanced by GM-CSF and mediated by the C-type lectins DEC-205/CD205, MMR/CD206, DCIR/CLEC4A, DCIR2, and Siglec-H.
| Antigen uptake | Antigen processing | MHC loading and presentation |
| Antigen uptake | ||
| DCIR/CLEC4A | DEC-205/CD205 | Siglec-H |
| DCIR2 | MMR/CD206 | Dendritic Cell Pathogen Recognition/Uptake |
| Antigen processing | |||
| Aminopeptidase LRAP/ERAP2 | Cathepsin D | Cathepsin H | Cathepsin X/Z/P |
| Aminopeptidase PILS/ARTS1 | Cathepsin F | Cathepsin L | IRAP |
| Cathepsin B | Cathepsin G | Cathepsin S | Proteasome Inhibitors |
| MHC loading and presentation | ||
| Beta 2-Microglobulin | Erp57/PDIA3 | Tapasin |
| Calreticulin | HLA Class I | |