Drescher J, Aron R
Hannover Medical School, Institute of Virology, Germany.
J Med Virol. 1999 Apr;57(4):397-404. doi: 10.1002/(sici)1096-9071(199904)57:4<397::aid-jmv12>3.0.co;2-r.
For influenza H1N1 strains, including some of their escape variants, the association of amino acid differences located at their hemagglutinin HA1 domains with their antigenic relationship was examined. The antigenic relationship was recorded in terms of the ratios of hemagglutination inhibition (HI) titers, the concentration of antibody molecules recognized by the virus, and the equilibrium constant of epitope-paratope interaction determined with heterologous virus compared to that found with homologous virus. The HI titers of antisera were found to depend primarily on the concentration of antibody molecules recognized by the virus and much less on the equilibrium constants. The avidity of antibody in sera raised against historically later strains with earlier strains was higher than vice versa. In contrast to the results obtained with antisera, the same concentration of monoclonal antibody directed to the Sb site of A/Brazil virus was recognized by both heterologous and homologous viruses, and the differences in HI titers observed were due to avidity changes only. Some of the amino acid differences located at each of the antigenic sites were found to be associated with a reduction in the HI titers and in the concentration of antibody molecules recognized by heterologous virus, whereas other differences in addition decreased the avidity of epitope-paratope interaction. Further amino acid differences decreased the avidity only. The strains tested differed also in their amino acids located outside the antigenic sites. However, an influence of these differences on the reaction of virus with antibody could not be evidenced. For the strains tested, the antigenic hemagglutinin drift occurred by reduction of the concentration of antibody molecules recognized by the virus and by avidity changes, which, in turn, were caused by exchanges of some key residues located at the antigenic sites.
对于甲型H1N1流感病毒株，包括其一些逃逸变体，研究了位于其血凝素HA1结构域的氨基酸差异与其抗原关系之间的关联。抗原关系通过血凝抑制（HI）效价的比值、病毒识别的抗体分子浓度以及与同源病毒相比用异源病毒测定的表位 - 抗原决定簇相互作用的平衡常数来记录。发现抗血清的HI效价主要取决于病毒识别的抗体分子浓度，而对平衡常数的依赖性要小得多。针对历史上较晚出现的毒株产生的血清与较早出现的毒株相比，其抗体亲和力更高，反之亦然。与抗血清的结果相反，针对A/巴西病毒Sb位点的相同浓度的单克隆抗体被异源和同源病毒均能识别，观察到的HI效价差异仅归因于亲和力的变化。发现在每个抗原位点的一些氨基酸差异与HI效价降低以及异源病毒识别的抗体分子浓度降低有关，而其他差异还会降低表位 - 抗原决定簇相互作用的亲和力。进一步的氨基酸差异仅降低亲和力。所测试的毒株在抗原位点之外的氨基酸也存在差异。然而，无法证明这些差异对病毒与抗体反应的影响。对于所测试的毒株，抗原性血凝素漂移是通过降低病毒识别的抗体分子浓度和亲和力变化而发生的，而这又是由位于抗原位点的一些关键残基的交换引起的。
