Novel blocking human IgG directed against the pentapeptide repeat motifs of Neisseria meningitidis Lip/H.8 and Laz lipoproteins.
Novel blocking human IgG directed against the pentapeptide repeat motifs of Neisseria meningitidis Lip/H.8 and Laz lipoproteins.
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DOI：
10.4049/jimmunol.1003623
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发表时间：
2011-04-15
期刊：
影响因子：
--
通讯作者：
Ram S
中科院分区：
文献类型：
--
作者：
Ray TD;Lewis LA;Gulati S;Rice PA;Ram S
抗体启动的补体依赖性杀伤有助于宿主防御侵袭性脑膜炎球菌病。来自未免疫个体的血清对B群脑膜炎球菌的杀菌活性差异很大。我们表明，从选定的个人中分离的IgG可以阻止杀死组B脑膜炎球菌的人血清，否则杀菌。该IgG还降低了针对B群脑膜炎球菌蛋白疫苗候选物因子H结合蛋白（fHbp）和奈瑟氏球菌表面蛋白A（NspA）的抗体的杀菌效力。免疫印迹显示，阻断IgG是针对脑膜炎球菌抗原称为H.8。当使用对应于H.8的合成肽或针对H.8的非阻断性mAb抑制阻断性Ab与脑膜炎球菌的结合时，在含有杀菌性mAb和人阻断性Ab的反应中脑膜炎球菌的杀伤恢复。此外，从靶生物体中遗传缺失H.8消除了阻断。封闭IgG的Fc区是封闭所必需的，因为F（ab）2片段无效。阻断需要IgG糖基化，因为用肽：N-聚糖酶（PNGase）去糖基化消除了阻断。完整的阻断IgG可减少抗fHbp mAb介导的C4 b沉积，但经PNGase处理的阻断IgG不能减少，表明阻断是由于抑制补体的经典途径所致。总之，我们已经确定了H.8作为脑膜炎球菌的目标，在人血清中的新型封闭抗体。这种阻断性Ab可能降低选择的抗B群脑膜炎球菌蛋白疫苗的效力。我们还提出，如果清除破坏性免疫原如H.8，含有外膜囊泡的脑膜炎球菌疫苗可能更有效。这是作者制作的手稿版本，已被《免疫学杂志》（The JI）接受出版。美国免疫学家协会(AAI)JI出版社拥有本手稿的版权。这份手稿尚未由联合执行机构进行编辑或编辑校对;因此可能与联合执行机构（在线和印刷版）公布的最终版本不同。AAI（JI）对作者制作的手稿版本或美国国立卫生研究院或任何其他第三方从中衍生的任何版本中的错误或遗漏不承担任何责任。记录的最终可引用版本可在www.jimmunol.org上找到。
Antibody-initiated complement-dependent killing contributes to host defenses against invasive meningococcal disease. Sera from non-immunized individuals vary widely in their bactericidal activity against group B meningococci. We show that IgG isolated from select individuals can block killing of group B meningococci by human sera that are otherwise bactericidal. This IgG also reduced the bactericidal efficacy of antibodies directed against the group B meningococcal protein vaccine candidates factor H-binding protein (fHbp) currently undergoing clinical trials, and Neisserial surface protein A (NspA). Immunoblots revealed that the blocking IgG was directed against a meningococcal antigen called H.8. Killing of meningococci in reactions containing bactericidal mAbs and human blocking Abs was restored when binding of blocking Ab to meningococci was inhibited using either synthetic peptides corresponding to H.8 or a non-blocking mAb against H.8. Further, genetic deletion of H.8 from target organisms abrogated blocking. The Fc region of the blocking IgG was required for blocking because F(ab)2 fragments were ineffective. Blocking required IgG glycosylation because deglycosylation with peptide:N-glycanase (PNGase) eliminated blocking. C4b deposition mediated by an anti-fHbp mAb was reduced by intact blocking IgG, but not by PNGase-treated blocking IgG, suggesting that blocking resulted from inhibition of classical pathway of complement. In conclusion, we have identified H.8 as a meningococcal target for novel blocking antibodies in human serum. Such blocking Ab may reduce the efficacy of select anti-group B meningococcal protein vaccines. We also propose that outer membrane vesicle-containing meningococcal vaccines may be more efficacious if purged of subversive immunogens such as H.8. This is an author-produced version of a manuscript accepted for publication in The Journal of Immunology (The JI). The American Association of Immunologists, Inc. (AAI), publisher of The JI, hold the copyright to this manuscript. This manuscript has not yet been copyedited or subjected to editorial proofreading by The JI; hence it may differ from the final version published in The JI (online and in print). AAI (The JI) is not liable for errors or omissions in this author-produced version of the manuscript or in any version-derived from it by the United States National Institutes of Health or any other third party. The final, citable version of record can be found at www.jimmunol.org.
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影响因子：
6.4
作者：
Hou, VC;Koeberling, O;Granoff, DM
通讯作者：
Granoff, DM
影响因子：
1.7
作者：
Baker, M G;Martin, D R;Lennon, D
通讯作者：
Lennon, D
影响因子：
3.1
作者：
Hou, VC;Moe, GR;Granoff, DM
通讯作者：
Granoff, DM
影响因子：
3.1
作者：
Fletcher, LD;Bernfield, L;Zlotnick, GW
通讯作者：
Zlotnick, GW
DOI：
10.1084/jem.129.6.1307
发表时间：
1969-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Goldschneider I;Gotschlich EC;Artenstein MS
通讯作者：
Artenstein MS