6JQ3

Crystal Structure of H2-Kb in complex with a DPAGT1 mutant peptide

Summary for 6JQ3

• Entry DOI: 10.2210/pdb6jq3/pdb
• Descriptor: H-2 class I histocompatibility antigen, K-B alpha chain, DPAGT1 mutant antigen SIIVFNLL, Beta-2-microglobulin, ... (4 entities in total)
• Functional Keywords: major histocompatibility complex, h2-kb, antigen, mouse, mhc, immune system
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 3
• Total formula weight: 44226.80

Authors

Bai, P.,Zhou, Q.,Wei, P.,Yin, L. (deposition date: 2019-03-28, release date: 2020-05-06, Last modification date: 2024-11-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.5 Å)