Table 1.
Structures of TCR–pMHC complexes involving cancer neoantigens.
| TCR–pMHC complex | PDB code (reference) | Neoepitope | Affinity wild-type |
Affinity mutant |
Basis for neoepitope immunogenicity |
|---|---|---|---|---|---|
| E8–TPIT28I–HLA-DR1 | 2IAM (18) | GELIGILNAAKVPAD | UD | >300 μM | Direct TCR contacts with mutation |
| G4–TPIT28I–HLA-DR1 | 4E41 (19) | GELIGILNAAKVPAD | UD | >300 μM | Direct TCR contacts with mutation |
| 12-6–p53R175H–HLA-A*02:01 | 6VRM (20) | HMTEVVRHC | UD | 1.1 μM | Direct TCR contacts with mutation |
| 38-10–p53R175H–HLA-A*02:01 | 6VRN (20) | HMTEVVRHC | UD | 39.9 μM | Direct TCR contacts with mutation |
| 1a2–p53R175H–HLA-A*02:01 | 6VQO (20) | HMTEVVRHC | UD | 16.2 μM | Direct TCR contacts with mutation |
| 6-11–p53R175H–HLA-A*02:01 | 7RM4 (21) | HMTEVVRHC | 214 μM | 3.5 μM | No direct TCR contacts with mutation Reduced energetic cost of desolvating mutation during TCR engagement |
| 9a–KRASG12D–HLA-C*08:02 | 6ULN (22) | GADGVGKSA | NA | 16 nM | Stabilization of pMHC ligand by anchor residue mutation |
| 9d–KRASG12D–HLA-C*08:02 | 6ULR (22) | GADGVGKSA | NA | 125 nM | Stabilization of pMHC ligand by anchor residue mutation |
| 10–KRASG12D–HLA-C*08:02 | 6UON (22) | GADGVGKSAL | NA | 6.7 μM | Stabilization of pMHC ligand by anchor residue mutation |
| JDI–KRASG12D–HLA-C*11:01 | 7PB2 (23) | VVVGADGVGK | UD | 63 μM | No direct TCR contacts with mutation Formation of new electrostatic interactions of mutant peptide with TCR |
| 1-2C–KRASG12V–HLA-A*11*01 | 8I5C (24) | VVGAVGVGK | 131 μM | 14 μM | Direct TCR contacts with mutation |
| 3-2E–KRASG12V–HLA-A*11*01 | 8I5D (24) | VVGAVGVGK | 42 μM | 28 μM | Direct TCR contacts with mutation |
| 302TIL–HHATp8F–HLA-A*02:06 | 6UK4 (25) | KQWLVWLFL | 200 μM | 9 μM | Conformational pre-organization of pMHC ligand by mutation |
| 3–PIK3CAH1047L–HLA-A*03:01 | 7RRG (26) | ALHGGWTTK | ND | 200 μM | Stabilization of pMHC ligand by anchor residue mutation |
| 4–PIK3CAH1047L–HLA-A*03:01 | 7L1D (26) | ALHGGWTTK | ND | 49 μM | Stabilization of pMHC ligand by anchor residue mutation |
UD, undetectable; NA, not applicable; ND, not determined.