Structural basis for oligoclonal T cell recognition of a shared p53 cancer neoantigen [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 577.2 Specific factors affecting ecology
• Thông tin xuất bản: Bethesda, Md. : Oak Ridge, Tenn. : National Institutes of Health (U.S.) ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2020
• Mô tả vật lý: Size: Article No. 2908 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 259859
• Chủ đề: 1. 60 applied life sciences

Tóm tắt

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.