首页> 外文期刊>Infection and immunity >A Monoclonal Antibody That Conveys In Vitro Killing and Partial Protection in Experimental Syphilis Binds a Phosphorylcholine Surface Epitope of Treponema pallidum
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A Monoclonal Antibody That Conveys In Vitro Killing and Partial Protection in Experimental Syphilis Binds a Phosphorylcholine Surface Epitope of Treponema pallidum

机译:在实验性梅毒中具有体外杀伤和部分保护作用的单克隆抗体与梅毒螺旋体的磷酸胆碱表面表位结合

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Immunization with purified Treponema pallidum outer membrane vesicles (OMV) has previously resulted in high-titer complement-dependent serum bactericidal activity. In this study, OMV immunization resulted in the isolation of a monoclonal antibody, M131, with complement-dependent killing activity. Passive immunization of rabbits with M131 administered intravenously conferred significant immunity demonstrated by the failure of syphilitic lesions to appear at 29% of intradermal challenge sites (7/24) and a mean delay of approximately 8 days to lesion appearance at the remaining sites (17/24). M131 not only bound to OMV and to the surfaces of intact motile T. pallidum cells but also bound to organisms whose outer membranes were removed, indicating both surface and subsurface locations for the killing target. This target was determined to be a T. pallidum lipid. Lipid extracted from T. pallidum and made into liposomes bound M131. Reverse-phase high-pressure liquid chromatography separation and fraction collection mass spectrometry (LC-MS+) of T. pallidum lipid showed that the target of M131 was phosphorylcholine. M131 binding required both liposome formation and a critical concentration of phospholipid containing phosphorylcholine, suggesting that the epitope has both a conformational and a compositional requirement. M131 did not react with red blood cells, which have phosphorylcholine-containing lipids in their exterior membrane leaflets, or with Venereal Disease Research Laboratory antigen that also contains phosphorylcholine, further indicating the specificity of M131. This is the first physical demonstration of an antigen on the T. pallidum surface and indication that such a surface antigen can be a target of immunity.
机译:纯化的梅毒螺旋体外膜囊泡(OMV)进行免疫接种以前可产生高滴度补体依赖性血清杀菌活性。在这项研究中,OMV免疫导致分离出具有补体依赖性杀伤活性的单克隆抗体M131。静脉内施用M131的兔的被动免疫赋予显着的免疫力,表现为梅毒损害未能出现在皮内攻击位点的29%(7/24),而其余部位的病变出现平均延迟了约8天(17 / 24)。 M131不仅与OMV结合,而且与完整的运动T的表面结合。苍白球细胞,但也与外膜被去除的生物结合,表明杀伤目标的表面和亚表面位置。确定该目标为 T。苍白脂。从 T中提取的脂质。苍白质并制成结合M131的脂质体。 T的反相高压液相色谱分离和馏分收集质谱(LC-MS +)。苍白脂显示,M131的靶标是磷酸胆碱。 M131结合需要脂质体的形成和临界浓度的含磷脂酰胆碱的磷脂,这表明表位既有构象又有组成要求。 M131不与在其外膜小叶中具有含磷酸胆碱的脂质的红细胞或与也含有磷酸胆碱的性病研究实验室抗原发生反应,这进一步表明了M131的特异性。这是 T上抗原的第一个物理证明。苍白球表面,表明这种表面抗原可能是免疫的靶标。

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