Cancer Immunotherapy: Antigen Presentation

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