Variations in the neutralizing and haemagglutination-inhibiting activities of five influenza A virus-specific IgGs and their antibody fragments
Variations in the neutralizing and haemagglutination-inhibiting activities of five influenza A virus-specific IgGs and their antibody fragments
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DOI：
10.1099/0022-1317-78-10-2431
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发表时间：
1997-10-01
影响因子：
3.8
通讯作者：
Dimmock, NJ
中科院分区：
文献类型：
--
作者：
Schofield, DJ;Stephenson, JR;Dimmock, NJ
比较了一组五种单克隆 IgG、它们的 F(ab')(2)、Fab 和 Fabs+ 抗小鼠 Fab 对 A 型流感病毒的中和和血凝抑制 (HI)，MAb 对血凝素的抗原位点 A、B 和 D 具有特异性。 IgG 的活性在摩尔基础上变化高达 6 倍，除了 HC58 的 HI 活性低 > 100 倍之外，这不是由于功能亲和力低，因为 HC58 具有第二高值 (nM)，如通过整个病毒粒子的平衡方法测定的，转换为 F(ab')(2) 减少了中和和 HI 仅 2 至 6 倍，表明 pc 区域几乎不参与这些过程，然而，与它们的 IgG 相比，所有 Fab 的中和活性和 HI 活性均较低，中和活性降低了 86 倍至 > 1912 倍，HI 活性降低了 13 倍至 > 69 倍。尽管下降，但它们的亲和力仍然很高，在 nM 范围内，通过添加抗 fab IgG 可以恢复三种 Fab（HC2、HC3W 和 HC61）的中和作用和 HI；然而，HC10 Fab+抗 Fab IgG 仍然没有可检测到的中和活性，但产生 HI，而 HC58 Fab+抗 Fab IgG 没有可检测到的 HI 活性，但中和程度与其 IgG 相同。根据其已知的作用机制讨论了抗体的不同特性：HI 通过空间阻断病毒与红细胞受体的附着，通过抑制附着后事件（HC2、HC10）来中和。和 HC61），数据表明单个 IgG 的抗病毒特性有多么可变。
Neutralization and haemagglutination-inhibition (HI) of a type A influenza virus by a panel of five monoclonal IgGs, their F(ab')(2)s, Fabs and Fabs+ anti-mouse Fab were compared, The MAbs were specific for antigenic sites A, B and D of the haemagglutinin. Activities of the IgGs varied by up to 6-fold on a molar basis, apart from the HI activity of HC58 which was > 100-fold lower, This was not due to low functional affinity as HC58 had the second highest value (nM) as determined by an equilibrium method with whole virions, Conversion to the F(ab')(2) reduced neutralization and HI by only 2- to 6-fold, indicating that the pc region had little involvement in these processes, However, all Fabs had low neutralization and HI activity compared with their IgGs, neutralization being reduced by 86 to > 1912-fold, and HI by 13 to > 69-fold. Although decreased, their affinities remained high, in the nM range, Neutralization and HI by three of the Fabs (HC2, HC3W and HC61) were restored by the addition of anti-fab IgG; however, HC10 Fab+anti-Fab IgG still had no detectable neutralization activity but gave HI, and HC58 Fab+anti-Fab IgG had no detectable HI activity but neutralized to the same extent as its IgG, The different properties of the antibodies are discussed in the light of their known mechanisms of action: HI by steric blocking of attachment of virus to the red cell receptor, and neutralization by the inhibition of post-attachment events (HC2, HC10 and HC61), The data demonstrate just how variable are the antiviral properties of individual IgGs.