8V4Z の概要
| エントリーDOI | 10.2210/pdb8v4z/pdb |
| 分子名称 | MHC class I antigen, Beta-2-microglobulin, LEU-PRO-PHE-GLU-LYS-SER-THR-ILE-MET, ... (7 entities in total) |
| 機能のキーワード | hla b*3501, np418 epitope, t cell immunity, glycoprotein, host-virus interaction, immune response, immune system |
| 由来する生物種 | Homo sapiens (human) 詳細 |
| タンパク質・核酸の鎖数 | 20 |
| 化学式量合計 | 375963.94 |
| 構造登録者 | |
| 主引用文献 | Quinones-Parra, S.M.,Gras, S.,Nguyen, T.H.O.,Farenc, C.,Szeto, C.,Rowntree, L.C.,Chaurasia, P.,Sant, S.,Boon, A.C.M.,Jayasinghe, D.,Rimmelzwaan, G.F.,Petersen, J.,Doherty, P.C.,Uldrich, A.P.,Littler, D.R.,Rossjohn, J.,Kedzierska, K. Molecular determinants of cross-strain influenza A virus recognition by alpha beta T cell receptors. Sci Immunol, 10:eadn3805-eadn3805, 2025 Cited by PubMed Abstract: Cross-reactive αβ T cell receptors (TCRs) recognizing multiple peptide variants can provide effective control of rapidly evolving viruses yet remain understudied. By screening 12 naturally occurring influenza-derived HLA-B*35:01-restricted nucleoprotein (NP) epitopes (B*35:01-NP) that emerged since 1918 within influenza A viruses, including 2024 A/H5N1 viruses, we identified functional broadly cross-reactive T cells universally recognizing NP variants. Binding studies demonstrated that TCR cross-reactivity was concomitant with diminished antigen sensitivity. Primary human B*35:01/NPCD8 T cell lines displayed reduced cross-reactivity in the absence of CD8 coreceptor binding, validating the low avidity of cross-reactive B*35:01-NPCD8 T cell responses. Six TCR-HLA-B*35:01/NP crystal structures showed how cross-reactive TCRs recognized multiple B*35:01/NP epitope variants. Specific TCR interactions were formed with invariant and conserved peptide-HLA features, thus remaining distal from highly varied positions of the NP epitope. Our study defines molecular mechanisms associated with extensive TCR cross-reactivity toward naturally occurring viral variants highly relevant to universal protective immunity against influenza. PubMed: 39919196DOI: 10.1126/sciimmunol.adn3805 主引用文献が同じPDBエントリー |
| 実験手法 | X-RAY DIFFRACTION (2.40000208775 Å) |
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