7SCO

Structure of H1 influenza hemagglutinin bound to Fab 310-39G10

7SCO の概要

• エントリーDOI: 10.2210/pdb7sco/pdb
• EMDBエントリー: 25040
• 分子名称: Hemagglutinin HA1 chain, Hemagglutinin HA2 chain, 310-39G10 Fab, Heavy Chain, ... (6 entities in total)
• 機能のキーワード: influenza, hemagglutinin, antibody, h1, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Influenza A virus (strain A/New Zealand:South Canterbury/35/2000 H1N1); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 265065.99

構造登録者

Torrents de la Pena, A.,Ward, A.B. (登録日: 2021-09-28, 公開日: 2022-08-24, 最終更新日: 2024-11-20)

主引用文献

Sangesland, M.,Torrents de la Pena, A.,Boyoglu-Barnum, S.,Ronsard, L.,Mohamed, F.A.N.,Moreno, T.B.,Barnes, R.M.,Rohrer, D.,Lonberg, N.,Ghebremichael, M.,Kanekiyo, M.,Ward, A.,Lingwood, D.
Allelic polymorphism controls autoreactivity and vaccine elicitation of human broadly neutralizing antibodies against influenza virus.
Immunity, 55:1693-1709.e8, 2022

PubMed Abstract: Human broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin stalk of group 1 influenza A viruses (IAVs) are biased for IGHV1-69 alleles that use phenylalanine (F54) but not leucine (L54) within their CDRH2 loops. Despite this, we demonstrated that both alleles encode for human IAV bnAbs that employ structurally convergent modes of contact to the same epitope. To resolve differences in lineage expandability, we compared F54 versus L54 as substrate within humanized mice, where antibodies develop with human-like CDRH3 diversity but are restricted to single V genes. While both alleles encoded for bnAb precursors, only F54 IGHV1-69 supported elicitation of heterosubtypic serum bnAbs following immunization with a stalk-only nanoparticle vaccine. L54 IGHV1-69 was unproductive, co-encoding for anergic B cells and autoreactive stalk antibodies that were cleared from B cell memory. Moreover, human stalk antibodies also demonstrated L54-dependent autoreactivity. Therefore, IGHV1-69 polymorphism, which is skewed ethnically, gates tolerance and vaccine expandability of influenza bnAbs.

PubMed: 35952670
DOI: 10.1016/j.immuni.2022.07.006

実験手法

ELECTRON MICROSCOPY (3.37 Å)