Figure 2.

Schematic representation of two extreme scenarios leading to either effective cytotoxic responses against a cancer cell (A) or immune evasion (B). A tumor-specific antigenic epitope or its N-terminal extended precursor is generated by the proteasome and transported into the ER. There, it is further processed by ERAP1/ERAP2 alleles. In case A, the “green” and “cyan” allele effectively generate the mature epitope (red line), which is then loaded onto nascent empty MHC class I and presented to the cell-surface, activating antigen-specific T cells. In case B, hyper-active or hypo-active ERAP1/ERAP2 alleles (in red and orange) either fail to produce the mature epitope or destroy it by generating peptides too small to bind onto MHC class I molecules. As a result, the epitope is not presented on the cell surface and no T cell activation occurs, facilitating immune evasion. The allelic state of ERAP1 and ERAP2 can therefore influence anti-tumor adaptive immune responses pre-disposing individuals to certain cancers by facilitating immune evasion at early stages of malignant development.