6MT6

Crystal Structure of HLA-B*37:01 in complex with NP338 influenza peptide

Summary for 6MT6

• Entry DOI: 10.2210/pdb6mt6/pdb
• Descriptor: HLA class I histocompatibility antigen, B-37 alpha chain, NP388 peptide, Beta-2-microglobulin, ... (5 entities in total)
• Functional Keywords: tcr, t cell, influenza, hla, hla-b18, hla-b37, hla-b44, viral mutation, cd8 t cells, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 45050.78

Authors

Gras, S. (deposition date: 2018-10-19, release date: 2019-02-13, Last modification date: 2024-10-23)

Primary citation

Grant, E.J.,Josephs, T.M.,Loh, L.,Clemens, E.B.,Sant, S.,Bharadwaj, M.,Chen, W.,Rossjohn, J.,Gras, S.,Kedzierska, K.
Broad CD8+T cell cross-recognition of distinct influenza A strains in humans.
Nat Commun, 9:5427-5427, 2018

PubMed Abstract: Newly-emerged and vaccine-mismatched influenza A viruses (IAVs) result in a rapid global spread of the virus due to minimal antibody-mediated immunity. In that case, established CD8 T-cells can reduce disease severity. However, as mutations occur sporadically within immunogenic IAV-derived T-cell peptides, understanding of T-cell receptor (TCRαβ) cross-reactivity towards IAV variants is needed for a vaccine design. Here, we investigate TCRαβ cross-strain recognition across IAV variants within two immunodominant human IAV-specific CD8 T-cell epitopes, HLA-B*37:01-restricted NP (B37-NP) and HLA-A*01:01-restricted NP (A1-NP). We find high abundance of cross-reactive TCRαβ clonotypes recognizing distinct IAV variants. Structures of the wild-type and variant peptides revealed preserved conformation of the bound peptides. Structures of a cross-reactive TCR-HLA-B37-NP complex suggest that the conserved conformation of the variants underpins TCR cross-reactivity. Overall, cross-reactive CD8 T-cell responses, underpinned by conserved epitope structure, facilitates recognition of distinct IAV variants, thus CD8 T-cell-targeted vaccines could provide protection across different IAV strains.

PubMed: 30575715
DOI: 10.1038/s41467-018-07815-5

Experimental method

X-RAY DIFFRACTION (1.31 Å)