HLA-C and cancer: An ideal immunization epitope undergoescross-presentation by MHC class I molecules to prime cytotoxic CD8+T cells, in addition to MHC class II presentation of longer sequencesto prime immune-memory CD4+ T cells (Figure 1A).6−10 The design of these epitopes is aided by immunopeptidomics combinedwith computational tools, which enable optimization of MHC-bindingaffinity11−13 and T cell receptor (TCR) specificity.14 Although these tools enable design of epitopesthat can be presented, particularly for personalized cancer vaccines,15 they provide little insight into designing theflanking residues.