Hernández Ana María, Rodríguez Mabel, López-Requena Alejandro, Beausoleil Irene, Pérez Rolando, Vázquez Ana Maria
Department of Antibody Engineering, Center of Molecular Immunology, P.O. Box 16040, Havana 11600, Cuba.
Immunobiology. 2005;210(1):11-21. doi: 10.1016/j.imbio.2005.02.002.
We have previously generated a murine anti-idiotype (Ab2) monoclonal antibody (mAb) to a murine Ab1 mAb, named P3, which selectively binds Neu-glycolyl (NeuGc)-sialic acid on several monosialo- and disialogangliosides, and also reacts with sulfatides and antigens expressed in human melanoma and breast tumors. This Ab2 mAb, designated as 1E10, induced anti-anti-idiotype antibodies (Ab3) in mice and cancer patients. These Ab3 generated by 1E10 mAb were characterized by bearing P3 mAb idiotopes (Ab3, Id +). But when the specificity of these Ab3 antibodies was tested, no specific humoral response against NeuGc-containing gangliosides was detected in sera from immunized mice. However, hyperimmune sera from melanoma and breast cancer patients vaccinated with this Ab2 mAb were able to react specifically with these gangliosides. The different expression of NeuGc-containing gangliosides in the normal tissues of mice and humans could explain these results. In order to demonstrate these findings in other animal species with a different NeuGc-sialic acid expression, we performed similar studies in monkeys and chickens. In monkeys, as in most mammals, NeuGc-containing gangliosides are self-antigens. In contrast, chickens, like humans, lack the expression of these antigens in normal tissues. Here we report that the antibody response against NeuGc-containing gangliosides induced by immunization with 1E10 mAb was completely different in both species. No specific antibody response against these gangliosides was detected in hyperimmune monkey sera. In contrast, a strong and specific Ab3 response against GM3(NeuGc) and GM2(NeuGc) gangliosides (Ab3, Ag+) was generated in chickens due to the administration of 1E10 mAb.
我们之前已针对一种名为P3的鼠源Ab1单克隆抗体（mAb）制备了一种鼠源抗独特型（Ab2）单克隆抗体，P3可选择性结合多种单唾液酸和双唾液酸神经节苷脂上的Neu-糖基化（NeuGc）唾液酸，还可与人类黑色素瘤和乳腺肿瘤中表达的硫脂及抗原发生反应。这种Ab2单克隆抗体命名为1E10，可在小鼠和癌症患者体内诱导产生抗抗独特型抗体（Ab3）。由1E10单克隆抗体产生的这些Ab3具有P3单克隆抗体独特型（Ab3，Id +）的特征。但在检测这些Ab3抗体的特异性时，在免疫小鼠的血清中未检测到针对含NeuGc神经节苷脂的特异性体液反应。然而，接种该Ab2单克隆抗体的黑色素瘤和乳腺癌患者的超免疫血清能够与这些神经节苷脂发生特异性反应。小鼠和人类正常组织中含NeuGc神经节苷脂的不同表达情况可以解释这些结果。为了在具有不同NeuGc唾液酸表达的其他动物物种中验证这些发现，我们在猴子和鸡身上进行了类似研究。在猴子中，与大多数哺乳动物一样，含NeuGc神经节苷脂是自身抗原。相比之下，鸡与人类一样，在正常组织中缺乏这些抗原的表达。在此我们报告，用1E10单克隆抗体免疫诱导的针对含NeuGc神经节苷脂的抗体反应在这两个物种中完全不同。在超免疫猴血清中未检测到针对这些神经节苷脂的特异性抗体反应。相反，由于给予1E10单克隆抗体，鸡体内产生了针对GM3（NeuGc）和GM2（NeuGc）神经节苷脂的强烈且特异性的Ab3反应（Ab3，Ag +）。
