Department of Virology, Nagoya City University Graduate School of Medical Science, Nagoya City, Aichi, Japan.
Microbiol Immunol. 2012 Feb;56(2):99-106. doi: 10.1111/j.1348-0421.2012.00412.x.
How the antibodies of individual convalescent human sera bind to each amino acid residue at the antigenic sites of hemagglutinin (HA) of influenza viruses, and how the antigenic drift strains of influenza viruses are selected by human sera, is not well understood. In our previous study, it was found by a binding assay with a chimeric HA between A/Kamata/14/91 (Ka/91) and A/Aichi/2/68 that convalescent human sera, following Ka/91 like (H3N2) virus infection, bind to antigenic site A of Ka/91 HA. Here using chimeric HAs possessing single amino acid substitutions at site A, it was determined how those human sera recognize each amino acid residue at antigenic site A. It was found that the capacity of human sera to recognize amino acid substitutions at site A differs from one person to another and that some amino acid substitutions result in all convalescent human sera losing their binding capacity. Among these amino acid substitutions, certain ones might be selected by chance, thus creating successive antigenic drift. Phylogenetic analysis of the drift strains of Ka/91 showed amino acid substitutions at positions 133, 135 and 145 were on the main stream of the phylogenetic tree. Indeed, all of the investigated convalescent sera failed to recognize one of them.
人们对于个体恢复期血清中的抗体如何与流感病毒血凝素（HA）抗原表位上的每个氨基酸残基结合，以及人类血清如何选择流感病毒抗原漂移株，知之甚少。在我们之前的研究中，通过对 A/Kamata/14/91（Ka/91）和 A/Aichi/2/68 之间嵌合 HA 的结合分析发现，在 Ka/91 样（H3N2）病毒感染后，恢复期血清与 Ka/91 HA 的抗原表位 A 结合。在这里，我们使用在抗原表位 A 处具有单个氨基酸取代的嵌合 HA，确定了这些人血清如何识别抗原表位 A 上的每个氨基酸残基。结果发现，人血清识别抗原表位 A 上氨基酸取代的能力因人而异，某些氨基酸取代会导致所有恢复期血清丧失结合能力。在这些氨基酸取代中，某些取代可能是偶然选择的，从而导致连续的抗原漂移。对 Ka/91 的漂移株进行系统进化分析表明，位置 133、135 和 145 的氨基酸取代处于系统进化树的主流。事实上，所有调查的恢复期血清都无法识别其中之一。
