6OPD

Crystal Structure of ILNAMIVKI peptide bound to HLA-A2

Summary for 6OPD

• Entry DOI: 10.2210/pdb6opd/pdb
• Related: 6PTB 6PTE
• Descriptor: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, Melanoma antigen variant, ... (7 entities in total)
• Functional Keywords: mhc, hla-a2, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 45343.01

Authors

Davancaze, L.M.,Arbuiso, A.,Baker, B.M. (deposition date: 2019-04-24, release date: 2019-09-04, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.791 Å)