6UJO

HHAT L75F Neoantigen Peptide KQWLVWLFL Presented by HLA-A206

6UJO の概要

• エントリーDOI: 10.2210/pdb6ujo/pdb
• 関連するPDBエントリー: 6UJQ 6UK2 6UK4
• 分子名称: MHC class I antigen, Beta-2-microglobulin, Protein-cysteine N-palmitoyltransferase HHAT, ... (4 entities in total)
• 機能のキーワード: neoantigen, peptide/mhc, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 45114.28

構造登録者

Devlin, J.R.,Baker, B.M.,Vander Kooi, C. (登録日: 2019-10-03, 公開日: 2020-08-19, 最終更新日: 2023-10-11)

主引用文献

Devlin, J.R.,Alonso, J.A.,Ayres, C.M.,Keller, G.L.J.,Bobisse, S.,Vander Kooi, C.W.,Coukos, G.,Gfeller, D.,Harari, A.,Baker, B.M.
Structural dissimilarity from self drives neoepitope escape from immune tolerance.
Nat.Chem.Biol., 16:1269-1276, 2020

PubMed Abstract: T-cell recognition of peptides incorporating nonsynonymous mutations, or neoepitopes, is a cornerstone of tumor immunity and forms the basis of new immunotherapy approaches including personalized cancer vaccines. Yet as they are derived from self-peptides, the means through which immunogenic neoepitopes overcome immune self-tolerance are often unclear. Here we show that a point mutation in a non-major histocompatibility complex anchor position induces structural and dynamic changes in an immunologically active ovarian cancer neoepitope. The changes pre-organize the peptide into a conformation optimal for recognition by a neoepitope-specific T-cell receptor, allowing the receptor to bind the neoepitope with high affinity and deliver potent T-cell signals. Our results emphasize the importance of structural and physical changes relative to self in neoepitope immunogenicity. Considered broadly, these findings can help explain some of the difficulties in identifying immunogenic neoepitopes from sequence alone and provide guidance for developing novel, neoepitope-based personalized therapies.

PubMed: 32807968
DOI: 10.1038/s41589-020-0610-1

実験手法

X-RAY DIFFRACTION (2.25 Å)