The isolation of human monoclonal antibodies with broadly neutralizing breadth can provide a promising countermeasure for influenza A viruses infection. Most broadly neutralizing antibodies against influenza A viruses bind to the conserved stem region or the receptor-binding cavity of hemagglutinin and the interaction is dominated by the heavy chain. The light chain, however, contributes few or no direct contacts to the antigen. Here we report an H3-clade neutralizing human monoclonal antibody, AF4H1K1, which recognizes the hemagglutinin glycoproteins of all group 2 influenza A viruses. This human monoclonal antibody has been obtained through the screening by pairing different heavy and light chains from an H7N9-infected patient based on the next-generation sequencing technology. Further structural studies revealed that light chains modulate the neutralizing spectrum by affecting the local conformation of heavy chains, instead of direct interaction with the antigen. These findings provide important clues to understand the molecular basis of light chains in antigen recognition and to explore the strategies in particular of the use of light chain modification to develop broadly protective monoclonal antibodies against influenza A viruses and other emerging viruses.

具有广泛中和宽度的人单克隆抗体的分离可以为甲型流感病毒感染提供有希望的对策。抗甲型流感病毒的最广泛中和抗体与血凝素的保守茎区域或受体结合腔结合，相互作用主要由重链决定。然而，轻链几乎不或根本不与抗原直接接触。在这里，我们报告了一种H3包中和人单克隆抗体AF4H1K1，该抗体识别所有2类甲型流感病毒的血凝素糖蛋白。通过基于下一代测序技术，通过对来自H7N9感染患者的不同重链和轻链进行配对，通过筛选获得了该人单克隆抗体。进一步的结构研究表明，轻链通过影响重链的局部构象而不是与抗原的直接相互作用来调节中和谱。这些发现为理解抗原识别中轻链的分子基础并探索策略特别是利用轻链修饰开发针对甲型流感病毒和其他新兴病毒的广泛保护性单克隆抗体提供了重要线索。