6VRN

T cell receptor-p53-HLA-A2 complex

Summary for 6VRN

• Entry DOI: 10.2210/pdb6vrn/pdb
• Related: 6vqo 6vr1 6vr5 6vrm
• Descriptor: MHC class I antigen, Beta-2-microglobulin, T-cell receptor 38-10, alfa chain, ... (6 entities in total)
• Functional Keywords: tcr complex, mhc, hla, adoptive cell therapy, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 98427.16

Authors

Wu, D.,Gallagher, D.T.,Gowthaman, R.,Pierce, B.G.,Mariuzza, R.A. (deposition date: 2020-02-08, release date: 2020-06-17, Last modification date: 2023-10-11)

Primary citation

Wu, D.,Gallagher, D.T.,Gowthaman, R.,Pierce, B.G.,Mariuzza, R.A.
Structural basis for oligoclonal T cell recognition of a shared p53 cancer neoantigen.
Nat Commun, 11:2908-2908, 2020

PubMed Abstract: Adoptive cell therapy (ACT) with tumor-specific T cells can mediate cancer regression. The main target of tumor-specific T cells are neoantigens arising from mutations in self-proteins. Although the majority of cancer neoantigens are unique to each patient, and therefore not broadly useful for ACT, some are shared. We studied oligoclonal T-cell receptors (TCRs) that recognize a shared neoepitope arising from a driver mutation in the p53 oncogene (p53R175H) presented by HLA-A2. Here we report structures of wild-type and mutant p53-HLA-A2 ligands, as well as structures of three tumor-specific TCRs bound to p53R175H-HLA-A2. These structures reveal how a driver mutation in p53 rendered a self-peptide visible to T cells. The TCRs employ structurally distinct strategies that are highly focused on the mutation to discriminate between mutant and wild-type p53. The TCR-p53R175H-HLA-A2 complexes provide a framework for designing TCRs to improve potency for ACT without sacrificing specificity.

PubMed: 32518267
DOI: 10.1038/s41467-020-16755-y

Experimental method

X-RAY DIFFRACTION (2.46 Å)