7SU9
KRAS-G12D specific TCR9a in complex with C*05-GADGVGKSL
Summary for 7SU9
| Entry DOI | 10.2210/pdb7su9/pdb |
| Descriptor | TCR9a alpha chain, TCR9a beta chain, MHC class I antigen, ... (9 entities in total) |
| Functional Keywords | tcr hla-c kras-g12d, immune system |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 95685.40 |
| Authors | Sim, M.J.W.,Sun, P.D. (deposition date: 2021-11-16, release date: 2022-06-08, Last modification date: 2024-10-23) |
| Primary citation | Sim, M.J.W.,Stotz, Z.,Lu, J.,Brennan, P.,Long, E.O.,Sun, P.D. T cells discriminate between groups C1 and C2 HLA-C. Elife, 11:-, 2022 Cited by PubMed Abstract: Dimorphic amino acids at positions 77 and 80 delineate HLA-C allotypes into two groups, C1 and C2, which associate with disease through interactions with C1 and C2-specific natural killer cell receptors. How the C1/C2 dimorphism affects T cell recognition is unknown. Using HLA-C allotypes that differ only by the C1/C2-defining residues, we found that KRAS-G12D neoantigen-specific T cell receptors (TCRs) discriminated between C1 and C2 presenting the same KRAS-G12D peptides. Structural and functional experiments, and immunopeptidomics analysis revealed that Ser77 in C1 and Asn77 in C2 influence amino acid preference near the peptide C-terminus (pΩ), including the pΩ-1 position, in which C1 favors small and C2 prefers large residues. This resulted in weaker TCR affinity for KRAS-G12D-bound C2-HLA-C despite conserved TCR contacts. Thus, the C1/C2 dimorphism on its own impacts peptide presentation and HLA-C-restricted T cell responses, with implications in disease, including adoptive T cell therapy targeting KRAS-G12D-induced cancers. PubMed: 35587797DOI: 10.7554/eLife.75670 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.99 Å) |
Structure validation
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