Chimeric anti-N-glycolyl-ganglioside and its anti-idiotypic MAbs:: Immunodominance of their variable regions
Chimeric anti-N-glycolyl-ganglioside and its anti-idiotypic MAbs:: Immunodominance of their variable regions
复制标题
DOI：
10.1089/153685903322328965
复制
发表时间：
2003-08-01
期刊：
影响因子：
--
通讯作者：
Vázquez, AM
中科院分区：
文献类型：
--
作者：
López-Requena, A;De Acosta, CM;Vázquez, AM
P3单克隆抗体（MAb）是一种特异性识别N-羟乙酰（NeuGc）-神经节苷脂和硫苷脂的鼠IgM。它还与人类乳腺肿瘤和黑色素瘤中表达的抗原反应。在同基因模型中，P3单抗能够引发强的抗独特型（Ab 2）抗体应答，即使在没有佐剂或载体蛋白的情况下。1 E10 MAb是一种对P3 MAb具有特异性的抗独特型抗体，已在同基因和同种异体动物中证明具有抗肿瘤作用。本文报道了人IgG（1）嵌合P3和1 E10抗体的构建，以及对鼠单克隆抗体主要特性的保持性的评价。嵌合P3抗体与GM 3（NeuGc）和GM 2（NeuGc）神经节苷脂特异性反应，而不与其乙酰化变体反应。此外，它强烈识别抗独特型1 E10单克隆抗体。嵌合1 E10抗体与P3单抗特异性反应。在用两种嵌合抗体免疫Balb/c小鼠后，我们能够证明其可变区的免疫优势。由两种抗体诱导的抗独特型应答是强的，并且在大多数小鼠中甚至显著高于抗同种型应答，尽管事实上70%的嵌合分子相对于动物模型是异种的。
P3 monoclonal antibody (MAb) is a murine IgM that specifically recognizes N-glycolyl (NeuGc)-gangliosides and sulfatides. It also reacts with antigens expressed in human breast tumors and melanoma. In syngeneic model, P3 MAb is able to elicit a strong anti-idiotypic (Ab2) antibody response, even in the absence of adjuvants or carrier proteins. 1E10 MAb is an anti-idiotypic antibody specific for P3 MAb that has demonstrated anti-tumoral effects in syngeneic and allogeneic animals. Here we report the construction of the human IgG(1) chimeric P3 and 1E10 antibodies, and the evaluation of the maintenance of the main properties of the murine MAbs. Chimeric P3 antibody specifically reacted with GM3(NeuGc) and GM2(NeuGc) gangliosides, and not with their acetylated variants. Also, it strongly recognized the anti-idiotypic 1E10 MAb. Chimeric 1E10 antibody specifically reacted with P3 MAb. Upon immunization of Balb/c mice with both chimeric antibodies, we were able to demonstrate the immunodominance of their variable regions. The anti-idiotypic response induced by both antibodies was strong and in most of the mice was even significantly higher than the anti-isotypic response, despite the fact that 70% of the chimeric molecule is xenogenic with respect to the animal model.