Enhanced binding of antibodies generated during chronic HIV infection to mucus component MUC16.
Enhanced binding of antibodies generated during chronic HIV infection to mucus component MUC16.
复制标题
在慢性HIV感染期间与粘液成分MUC16产生的抗体的结合增强。
作者：
HIV通过粘膜屏障的传播占全世界HIV感染的大多数。因此，旨在增强这些部位的保护性免疫的努力是重中之重，包括增加粘膜部位的病毒特异性抗体（Ab）和抗病毒活性。粘蛋白，包括最大的细胞相关粘蛋白MUC 16，有助于形成粘液，为进入的病原体提供物理屏障。在这里，我们描述了抗体和MUC 16之间的自然相互作用，这种相互作用在特定的疾病环境中得到增强，例如慢性HIV感染。与MUC 16的结合不依赖于IgG亚类，但与较短的Ab聚糖谱密切相关，无半乳糖基化（G 0）Ab与MUC 16的结合最高。在MUC 16敲低后，Ab与上皮细胞的结合减少，并且MUC 16 N-连接的聚糖对于结合是关键的。此外，无半乳糖基化的VRC 01在MUC 16中更有效地捕获HIV。这些数据指出了一个新的机会，可以通过Fc糖基化的变化将Abs靶向MUC 16，从而在粘膜部位富集Abs，从而可能阻止病毒移动并将病毒隔离在远离上皮边缘的地方。因此，下一代疫苗或单克隆治疗剂可以通过调节Ab糖基化以促进Ab在粘膜屏障处的富集来增强保护性免疫。
Transmission of HIV across mucosal barriers accounts for the majority of HIV infections worldwide. Thus, efforts aimed at enhancing protective immunity at these sites are a top priority, including increasing virus-specific antibodies (Abs) and antiviral activity at mucosal sites. Mucin proteins, including the largest cell-associated mucin, MUC16, help form mucus to provide a physical barrier to incoming pathogens. Here we describe a natural interaction between Abs and MUC16 that is enhanced in specific disease settings such as chronic HIV infection. Binding to MUC16 was independent of IgG subclass, but strongly associated with shorter Ab glycan profiles, with agalactosylated (G0) Abs demonstrating the highest binding to MUC16. Binding of Abs to epithelial cells was diminished following MUC16-knockdown, and the MUC16 N-linked glycans were critical for binding. Further, agalactosylated VRC01 captured HIV more efficiently in MUC16. These data point to a novel opportunity to enrich Abs at mucosal sites by targeting Abs to MUC16 through changes in Fc-glycosylation, potentially blocking viral movement and sequestering the virus far from the epithelial border. Thus, next-generation vaccines or monoclonal therapeutics may enhance protective immunity by tuning Ab glycosylation to promote the enrichment of Abs at mucosal barriers.
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影响因子：
7.3
作者：
Frenzel A;Hust M;Schirrmann T
通讯作者：
Schirrmann T
急性感染后FC和FAB介导的HIV-1特异性抗体活性的独立进化。
影响因子：
5.4
作者：
Dugast, Anne-Sophie;Stamatatos, Leonidas;Tonelli, Andrew;Suscovich, Todd J.;Licht, Anna F.;Mikell, Iliyana;Ackerman, Margaret E.;Streeck, Hendrik;Klasse, P. J.;Moore, John P.;Alter, Galit
通讯作者：
Alter, Galit
影响因子：
4.4
作者：
Blalock, Timothy D.;Spurr-Michaud, Sandra J.;Gipson, Ilene K.
通讯作者：
Gipson, Ilene K.
DOI：
10.1097/00004347-198303000-00005
发表时间：
1983-01-01
影响因子：
2.4
作者：
KABAWAT, SE;BAST, RC;COLVIN, RB
通讯作者：
COLVIN, RB
影响因子：
2.9
作者：
DEISENHOFER, J
通讯作者：
DEISENHOFER, J