Complement component C1q enhances the biological activity of influenza virus hemagglutinin-specific antibodies depending on their fine antigen specificity and heavy-chain isotype
Complement component C1q enhances the biological activity of influenza virus hemagglutinin-specific antibodies depending on their fine antigen specificity and heavy-chain isotype
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DOI：
10.1128/jvi.76.3.1369-1378.2002
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发表时间：
2002-02-01
影响因子：
5.4
通讯作者：
Gerhard, W
中科院分区：
文献类型：
--
作者：
Feng, JQ;Mozdzanowska, K;Gerhard, W
我们先前观察到，选定的流感病毒血凝素(HA)特异性单抗(MAb)在体外对病毒中和(VN)活性较差，给SCID小鼠后，体内VN活性显著增强。同样的抗体在体外用SCID小鼠未灭活的血清进行测试时，也显示出更好的VN活性。为了确定抗体依赖的性质和有助于增强抗体活性的血清成分，我们筛选了一大组RA特异性单抗，在未灭活小鼠血清(NMS)存在的情况下进行血凝抑制(HI)。我们发现，NMS增强Ell活性依赖于抗体的良好特异性(抗原区CB/E>；Ca/A，D>；Sa，SB/B)，其重链亚型(免疫球蛋白G2[IgG2]和GT；IgG3；IgG1和IgM阴性)，以及在一定程度上也取决于其来源(初级反应和记忆反应)。平均而言，从初级应答中分离到的Cb/E特异性单抗的HI活性提高了20倍。VN活性显著增强，但强度低于HI活性。增强作用(I)被热灭活(30min，56℃)破坏；(R)不需要中央补体成分C3；(Iii)用抗C1q处理血清可取消；(Iv)可用纯化的C1q复制，C1q是第一补体成分C1的结合部分。我们认为，这是第一次描述C1q介导的抗病毒抗体活性的直接增强。
We have previously observed that selected influenza virus hemagglutinin (HA)-specific monoclonal antibodies (MAbs) with poor virus-neutralizing (VN) activity in vitro exhibited greatly enhanced VN activity in vivo after administration to SCID mice. The same Abs displayed improved VN activity also when tested in vitro in the presence of noninactivated serum from SCID mice. To identify Ab-dependent properties and serum components that contributed to enhancement of Ab activity, we screened a large panel of RA-specific MAbs for hemagglutination inhibition (HI) in the presence of noninactivated serum from naive mice (NMS). We found that Ell activity was enhanced by NMS depending on the Ab's fine specificity (antigenic region Cb/E > Ca/A,D > Sa,Sb/B), its heavy-chain isotype (immunoglobulin G2 [IgG2] > IgG3; IgG1 and IgM negative), and to some extent also on its derivation (primary response > memory response). On average, the HI activity of Cb/E-specific MAbs of the IgG2 isotype isolated from the primary response was enhanced by 20-fold. VN activity was enhanced significantly but less strongly than HI activity. Enhancement (i) was destroyed by heat inactivation (30 min, 56degreesC); (R) did not require C3, the central complement component; (iii) was abolished by treatment of serum with anti-C1q; and (iv) could be reproduced with purified C1q, the binding moiety of C1, the first complement component. We believe that this is the first description of a direct C1q-mediated enhancement of antiviral Ab activities.