The first structural studies of TCR recognition of a cancer neoantigen involved two tumor-specific TCRs (E8 and G4) isolated from TILs of a melanoma patient in complex with the MHC class II molecule HLA-DR1 and a mutated self-peptide derived from the glycolytic enzyme triosephosphate isomerase (TPI) (Table 1) (18, 19). Here, TPI1 is linked to cancer.