9DY8

Crystal structure of HLA-B*18:01 in complex with PEMTFFSVK, an 9-mer epitope from Influenza B

Summary for 9DY8

• Entry DOI: 10.2210/pdb9dy8/pdb
• Descriptor: MHC class I antigen, Beta-2-microglobulin, RNA-directed RNA polymerase catalytic subunit, ... (6 entities in total)
• Functional Keywords: leukocyte antigen, major histocompatibility complex, hla-b*18:01, influenza a, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 45336.09

Authors

Murdolo, L.D.,Maddumage, J.C.,Gras, S. (deposition date: 2024-10-13, release date: 2025-08-13)

Primary citation

Murdolo, L.D.,Liwei Leong, S.,Maddumage, J.C.,Mifsud, N.A.,Chatzileontiadou, D.S.M.,Grant, E.J.,Gras, S.
Characterisation of an influenza B virus-derived peptide presented by HLA-B*18:01.
Biochem.J., 482:811-820, 2025

PubMed Abstract: The influenza B virus (IBV) can pose a significant threat to global health. Despite this, IBV is understudied compared with influenza A virus (IAV). CD8+ T cells have proven highly effective in reducing influenza disease severity. In addition, pre-existing immune responses towards IAV epitopes may provide protection against homologous IBV-derived peptides due to T cell cross-reactivity. To exploit the advantages of T cells for future vaccine developments, a better understanding of the IBV-derived peptide presentation by the highly polymorphic human leukocyte antigen (HLA) is required. We previously determined that the IAV-derived PB1177-A peptide was presented by the HLA-B*18:01 molecule and induced CD8+ T cell responses. Here, we assessed the PB1177-A IBV homologue (PB1177-B). Intracellular cytokine staining assays showed that PB1177-B was unable to activate CD8+ T cells from several HLA-B*18:01+ samples tested. We determined that the IAVand IBV-derived PB1177 adopted different stability and conformation in the cleft of HLA-B*18:01. Molecular dynamics analysis on the crystal structure showed that PB1177-B had a central flexible region with a large hydrophobic patch formed by two phenylalanine residues, not present in PB1177-A. The flexibility and the lower stability of the HLA-B*18:01-PB1177-B complex may hinder CD8+ T cell receptor binding, underpinning the lack of CD8+ T cell activation observed. This provides additional insights into the differences between IAVand IBV-specific CD8+ T cell responses.

PubMed: 40587260
DOI: 10.1042/BCJ20240739

Experimental method

X-RAY DIFFRACTION (2 Å)