Gangliosides, Ab1 and Ab2 antibodies -: III.: The idiotype of anti-ganglioside mAb P3 is immunogenic in a T cell-dependent manner

Gangliosides, Ab1 and Ab2 antibodies -: III.: The idiotype of anti-ganglioside mAb P3 is immunogenic in a T cell-dependent manner
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DOI:
10.1016/j.molimm.2007.01.010
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发表时间:
2007-04-01
影响因子:
3.6
通讯作者:
Burrone, Oscar R.
Burrone, Oscar R.
中科院分区:
医学3区
文献类型:
--
作者:
Lopez-Requena, Alejandro;Bestagno, Marco;Burrone, Oscar R.

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P3 mAb是一种IgM单克隆抗体,对含N-羟乙酰神经节苷脂具有特异性。P3独特型的免疫原性先前已通过用纯化的鼠IgM或鼠-人嵌合IgG抗体免疫同基因BALB/c小鼠进行了描述。本文研究了DNA免疫对P3单克隆抗体独特型的抗体应答。我们使用了由scFv形式的独特型组成的小免疫蛋白(SIP),其共价连接到γ 1CH 3(鼠IgG 1的自二聚化结构域)。先前已证明SIP适合诱导特异性抗独特型应答。通过基因枪免疫,偶尔会产生多特异性反应,特别是P3独特型。单次DNA注射足以诱导强烈且持久的抗P3独特型应答。此外,通过用重组腺相关病毒递送相同的DNA构建体,证明了P3独特型的独特免疫原性。免疫同种异体C57 BL/6和无胸腺BALB/c小鼠后,P3特异性抗独特型抗体的缺乏表明了抗P3独特型应答中T细胞的需求。(c)2007爱思唯尔有限公司版权所有。
P3 mAb is an IgM monoclonal antibody specific for N-glycolyl-containing gangliosides. The immunogenicity of the P3 idiotype has been previously described by immunizing syngeneic BALB/c mice with the purified murine IgM or the mouse-human chimeric IgG antibody. In the present work we study the antibody response against the idiotype of P3 mAb through immunization with DNA. We used small immune proteins (SIP) consisting on the idiotype in the scFv format, covalently linked to gamma 1CH3, the self-dimerizing domain of murine IgG1. SIPs were previously shown to be appropriate to induce specific anti-idiotypic responses. By gene gun immunization, a polyspecific response was occasionally generated, particularly with the P3 idiotype. A single shot of DNA was sufficient to induce a strong and long-lasting anti-P3 idiotype response. In addition, by delivery of the same DNA construct with a recombinant adeno-associated virus the unique immunogenicity of the P3 idiotype was demonstrated. The requirement of T cells in the anti-P3 idiotype response was indicated by the lack of P3-specific anti-idiotypic antibodies following immunization of both, allogeneic C57BL/6 and athymic BALB/c mice. (c) 2007 Elsevier Ltd. All rights reserved.