Crystal Structure of HLA-B*37:01 in complex with NP338-V6L influenza peptideCrystal Structure of HLA-B*37:01 in complex with NP338-V6L influenza peptide

Structural highlights

6mt5 is a 3 chain structure with sequence from Homo sapiens and Unidentified influenza virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.55Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

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 (TCRalphabeta) cross-reactivity towards IAV variants is needed for a vaccine design. Here, we investigate TCRalphabeta cross-strain recognition across IAV variants within two immunodominant human IAV-specific CD8(+) T-cell epitopes, HLA-B*37:01-restricted NP338-346 (B37-NP338) and HLA-A*01:01-restricted NP44-52 (A1-NP44). We find high abundance of cross-reactive TCRalphabeta 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-NP338 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.

Broad CD8(+) T cell cross-recognition of distinct influenza A strains in humans.,Grant EJ, Josephs TM, Loh L, Clemens EB, Sant S, Bharadwaj M, Chen W, Rossjohn J, Gras S, Kedzierska K Nat Commun. 2018 Dec 21;9(1):5427. doi: 10.1038/s41467-018-07815-5. PMID:30575715[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Grant EJ, Josephs TM, Loh L, Clemens EB, 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. 2018 Dec 21;9(1):5427. doi: 10.1038/s41467-018-07815-5. PMID:30575715 doi:http://dx.doi.org/10.1038/s41467-018-07815-5

6mt5, resolution 1.55Å

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