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8Y74

Crystal structure of 9-mer peptide from H9N2 avian influenza virus in complex with BF2*0201

Summary for 8Y74
Entry DOI10.2210/pdb8y74/pdb
DescriptorMHC class I alpha chain 2, Beta-2-microglobulin, Polymerase basic protein 2, ... (4 entities in total)
Functional Keywordschicken mhc, t cell recognition, immune system
Biological sourceGallus gallus (chicken)
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Total number of polymer chains6
Total formula weight87013.12
Authors
Jia, Y.S.,Ma, M.L.,Liao, M.,Dai, M.M. (deposition date: 2024-02-03, release date: 2024-07-10, Last modification date: 2025-01-15)
Primary citationJia, Y.,Wu, Q.,Li, Y.,Ma, M.,Song, W.,Chen, R.,Yao, Y.,Nair, V.,Zhang, N.,Liao, M.,Dai, M.
Revealing novel and conservative T-cell epitopes with MHC B2 restriction on H9N2 avian influenza virus (AIV).
J.Biol.Chem., 300:107395-107395, 2024
Cited by
PubMed Abstract: B2 haplotype major histocompatibility complex (MHC) has been extensively reported to confer resistance to various avian diseases. But its peptide-binding motif is unknown, and the presenting peptide is rarely identified. Here, we identified its peptide-binding motif (X-A/V/I/L/P/S/G-X-X-X-X-X-X-V/I/L) in vitro using Random Peptide Library-based MHC I LC-MS/MS analysis. To further clarify the structure basis of motif, we determined the crystal structure of the BF2∗02:01-PB2 complex at 1.9 Å resolution. We found that BF2∗02:01 had a relatively wide antigen-binding groove, and the structural characterization of pockets was consistent with the characterization of peptide-binding motif. The wider features of the peptide-binding motif and increased number of peptides bound by BF2∗02:01 than BF2∗04:01 might resolve the puzzles for the presence of potential H9N2 resistance in B2 chickens. Afterward, we explored the H9N2 avian influenza virus (AIV)-induced cellular immune response in B2 haplotype chickens in vivo. We found that ratio of CD8 T cell and kinetic expression of cytotoxicity genes including Granzyme K, interferon-γ, NK lysin, and poly-(ADP-ribose) polymerase in peripheral blood mononuclear cells were significantly increased in defending against H9N2 AIV infection. Especially, we selected 425 epitopes as candidate epitopes based on the peptide-binding motif and further identified four CD8 T-cell epitopes on H9N2 AIV including NS1, PB2, NP, and NP via ELI-spot interferon-γ detections after stimulating memory lymphocytes with peptides. More importantly, these epitopes were found to be conserved in H7N9 AIV and H9N2 AIV. These findings provide direction for developing effective T cell epitope vaccines using well-conserved internal viral antigens in chickens.
PubMed: 38768812
DOI: 10.1016/j.jbc.2024.107395
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.9 Å)
Structure validation

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