6OPD

Crystal Structure of ILNAMIVKI peptide bound to HLA-A2

6OPD の概要

• エントリーDOI: 10.2210/pdb6opd/pdb
• 関連するPDBエントリー: 6PTB 6PTE
• 分子名称: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, Melanoma antigen variant, ... (7 entities in total)
• 機能のキーワード: mhc, hla-a2, 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: 45343.01

構造登録者

Davancaze, L.M.,Arbuiso, A.,Baker, B.M. (登録日: 2019-04-24, 公開日: 2019-09-04, 最終更新日: 2023-10-11)

主引用文献

Riley, T.P.,Keller, G.L.J.,Smith, A.R.,Davancaze, L.M.,Arbuiso, A.G.,Devlin, J.R.,Baker, B.M.
Structure Based Prediction of Neoantigen Immunogenicity.
Front Immunol, 10:2047-2047, 2019

PubMed Abstract: The development of immunological therapies that incorporate peptide antigens presented to T cells by MHC proteins is a long sought-after goal, particularly for cancer, where mutated neoantigens are being explored as personalized cancer vaccines. Although neoantigens can be identified through sequencing, bioinformatics and mass spectrometry, identifying those which are immunogenic and able to promote tumor rejection remains a significant challenge. Here we examined the potential of high-resolution structural modeling followed by energetic scoring of structural features for predicting neoantigen immunogenicity. After developing a strategy to rapidly and accurately model nonameric peptides bound to the common class I MHC protein HLA-A2, we trained a neural network on structural features that influence T cell receptor (TCR) and peptide binding energies. The resulting structurally-parameterized neural network outperformed methods that do not incorporate explicit structural or energetic properties in predicting CD8 T cell responses of HLA-A2 presented nonameric peptides, while also providing insight into the underlying structural and biophysical mechanisms governing immunogenicity. Our proof-of-concept study demonstrates the potential for structure-based immunogenicity predictions in the development of personalized peptide-based vaccines.

PubMed: 31555277
DOI: 10.3389/fimmu.2019.02047

実験手法

X-RAY DIFFRACTION (1.791 Å)