Knossow M, Daniels R S, Douglas A R, Skehel J J, Wiley D C
Nature. 1984;311(5987):678-80. doi: 10.1038/311678a0.
Antigenic variation in the haemagglutinin (HA) glycoprotein of influenza virus is associated with recurrent epidemics of respiratory disease in man (for review see ref. 1). We have examined the size of structural changes necessary to alter the antigenicity of HA by determining the three-dimensional structure of the HA from an antigenic mutant containing a single amino acid substitution which was selected by growth of virus in the presence of monoclonal antibodies. Here we present evidence that the simple addition of an amino acid side chain which results in only minor local distortions of the structure of the HA is sufficient structural alteration for a virus to escape neutralization by a monoclonal antibody. Our results also demonstrate that single amino acid substitutions can cause only local changes in the HA structure, verifying the assumption made in several studies to locate antigenic sites on the HA and other molecules, and indicate that proposals of large conformational changes to account for variations in HA antigenicity are unnecessary in this case. The structure of the variant antigen has independently been successfully predicted (M. Karplus, personal communication).
流感病毒血凝素（HA）糖蛋白的抗原变异与人呼吸系统疾病的反复流行有关（综述见参考文献1）。我们通过测定一个抗原突变体HA的三维结构，研究了改变HA抗原性所需的结构变化大小，该突变体含有一个单氨基酸取代，是在单克隆抗体存在下通过病毒生长筛选出来的。在此我们提供证据表明，仅导致HA结构轻微局部扭曲的一个氨基酸侧链的简单添加，就足以使病毒逃避单克隆抗体的中和作用。我们的结果还表明，单氨基酸取代只会引起HA结构的局部变化，证实了在多项研究中为确定HA和其他分子上的抗原位点所做的假设，并表明在这种情况下，无需用大的构象变化来解释HA抗原性的变异。变异抗原的结构已独立成功预测（M. 卡尔普斯，个人交流）。
