6MTL

Crystal Structure of HLA-B*44:05 in complex with NP338 influenza peptide

6MTL の概要

• エントリーDOI: 10.2210/pdb6mtl/pdb
• 分子名称: MHC class I antigen, Beta-2-microglobulin, NP338 peptide, ... (5 entities in total)
• 機能のキーワード: tcr, t cell, influenza, hla, hla-b18, hla-b37, hla-b44, viral mutation, cd8 t cells, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 44961.83

構造登録者

Gras, S. (登録日: 2018-10-19, 公開日: 2019-02-13, 最終更新日: 2024-10-16)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.35 Å)