6JTP

Crystal structure of HLA-C08 in complex with a tumor mut9m peptide

6JTP の概要

• エントリーDOI: 10.2210/pdb6jtp/pdb
• 分子名称: HLA class I antigen, Cw8.2 alpha chain, Beta-2-microglobulin, 9-mer peptide, ... (4 entities in total)
• 機能のキーワード: major histocompatibility complex, antigen, hla, 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: 44112.73

構造登録者

Bai, P.,Zhou, Q.,Wei, P.,Lei, Y. (登録日: 2019-04-11, 公開日: 2020-04-15, 最終更新日: 2024-10-23)

主引用文献

Bai, P.,Li, Y.,Zhou, Q.,Xia, J.,Wei, P.C.,Deng, H.,Wu, M.,Chan, S.K.,Kappler, J.W.,Zhou, Y.,Tran, E.,Marrack, P.,Yin, L.
Immune-based mutation classification enables neoantigen prioritization and immune feature discovery in cancer immunotherapy.
Oncoimmunology, 10:1868130-1868130, 2021

PubMed Abstract: Genetic mutations lead to the production of mutated proteins from which peptides are presented to T cells as cancer neoantigens. Evidence suggests that T cells that target neoantigens are the main mediators of effective cancer immunotherapies. Although algorithms have been used to predict neoantigens, only a minority are immunogenic. The factors that influence neoantigen immunogenicity are not completely understood. Here, we classified human neoantigen/neopeptide data into three categories based on their TCR-pMHC binding events. We observed a conservative mutant orientation of the anchor residue from immunogenic neoantigens which we termed the "NP" rule. By integrating this rule with an existing prediction algorithm, we found improved performance in neoantigen prioritization. To better understand this rule, we solved several neoantigen/MHC structures. These structures showed that neoantigens that follow this rule not only increase peptide-MHC binding affinity but also create new TCR-binding features. These molecular insights highlight the value of immune-based classification in neoantigen studies and may enable the design of more effective cancer immunotherapies.

PubMed: 33537173
DOI: 10.1080/2162402X.2020.1868130

実験手法

X-RAY DIFFRACTION (1.9 Å)