Studies on Immunogenicity of -2,8-Linked N-Glycolylneuraminic Acid Polymers

-2,8-连接N-甘醇神经氨酸聚合物的免疫原性研究

• 批准号: 60580125
• 负责人: INOUE Yasuo
• 金额: $ 0.83万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-60580125/
• 关键词: Polysialoglycoproteins; Anti-<alpha>-2,8-linked polysialic acid) antibody; Anti-(polyNeuAc) antibody; Anti-(polyNeuGc) antibody; ポリシアル酸の抗原性; 抗(8NeuAcα2→)n抗体; 抗(8NeuGcα2→)n糖タンパク質抗体; 抗ポリシアル酸抗体の抗原特異性; 新しいシアル酸アナログ(デアミノノイラミン酸)

In 1978, Inoue and Iwasaki discovered a novel class of sialoglycoproteins in rainbow trout eggs. The most striking feature of these glycoproteins is the presence of oligo(poly)sialyl chains, and we named them polysialoglycoproteins (PSGP). We have shown that PSGP is a ubiquitous component of the eggs of all species of salmonid fishes examined. This study was undertaken to elicit antibodies against polysialic acids because <alpha>-2,8-linked homopolymer of N-acetylneuraminic acid (NeuAc) structure occurring in the group B meningococci (Neisseria meningitidis) is pathogenic. <alpha>-2,8-Linked poly(NeuAc) is known to be extremely poor immunogen in various animals including human. Rainbow trout egg PSGP contains exclusively N-glycolylneuraminic acid (NeuGc), so that we used it as the immunogen to raise <alpha>-2,8-linked poly(NeuGc) antibodies in rabbits and BALB/c mice. We continued the antigen injection for 16 months, but there was np detectable antibodies in the serum of all animals us … More ed. The observed poor immunogenicity is ascribed, at least in part, to the presence of molecules having similar or identical structures in the host animals so that immunization would likely be suppressed by immune tolerance. Recently, we succeeded in eliciting anti-(rainbow trout PSGP) antiserum in chicken. We also examined the immunoreactivity of <alph>-2,8-linked poly(NeuGc) chains against a unique antiserum ("H-46"), obtained by J.B.Robbins (N.I.H.) after taking for 7 years by immunizing a horse using formalin-treated group B meningococci as immunogen. H.46 antiserum containing polyclonal IgM antibodies has been proven not to form immunoprecipitin bands against <alpha>-2,8-linked poly(NeuGc). It can thus be concluded that H.46 binds specifically to <alpha>-2,8-linked poly(NeuAc) and can onlybe used as a probe for poly(NeuAc). In this respect, our results on chicken, though preliminary, may provide the specific antibody against poly(NeuGc) which may possibly be used as a diagnostic tool for detecting poly(NeuGc) in a variety of animal tissues. Less

1978年，井上和岩崎在虹鲑卵中发现了一种新的唾液糖蛋白。这些糖蛋白最显著的特征是存在寡聚唾液酸链，我们将它们命名为聚唾液酸糖蛋白(PSGP)。我们已经证明PSGP是所有被研究的鲑科鱼类卵子中普遍存在的成分。由于B组脑膜炎双球菌(Neisseria Meningitidis)中的N-乙酰神经氨酸(NeuAc)结构的-lt；α&gt；-2，8-连接均聚物(NeuAc)是致病的，因此本研究旨在诱导针对聚唾液酸的抗体。已知&lt；α&gt；-2，8-连接的聚(NeuAc)在包括人类在内的各种动物中是极差的免疫原。虹鲑卵PSGP只含有N-羟基神经氨酸(NeuGc)，因此我们用它作为免疫原，在兔和BALB/c小鼠中制备了-lt；α&Gt；-2，8-多聚(NeuGc)抗体。我们继续注射抗原16个月，但在所有动物的血清中都有NP可检测到的抗体美国…。更多的爱德。观察到的低免疫原性至少部分归因于宿主动物中存在具有相似或相同结构的分子，因此免疫可能会受到免疫耐受的抑制。最近，我们成功地在鸡体内诱导出了抗虹鲑鱼PSGP的抗血清。我们还检测了~lt；alph&gt；-2，8-连接的聚(NeuGc)链对J.B.Robbins(N.I.H.)获得的一种独特的抗血清(“H-46”)的免疫反应性。用福尔马林处理过的B群脑膜炎双球菌作为免疫原免疫马7年后。含有多克隆IgM抗体的H.46抗血清已被证明不能形成抗-lt；α&gt；-2，8-连接的聚(NeuGc)的免疫受体条带。因此，可以得出结论：H.46与-lt；α&gt；-2，8-连接的聚(NeuAc)特异结合，只能作为聚(NeuAc)的探针。在这方面，我们在鸡身上的结果虽然是初步的，但可能提供针对聚(NeuGc)的特异性抗体，该抗体可能被用作在各种动物组织中检测聚(NeuGc)的诊断工具。较少

项目成果

Ken Kitajima;Sadako Inoue;Yasuo Inoue: THE JOURNAL OF BIOLOGICAL CHEMISTRY. (1988)

Ken Kitajima；Sadako Inoue；Yasuo Inoue：生物化学杂志。

Ken KITAJIMA: Science.

北岛健：科学。

Sadako Inoue;Yasuo Inoue: SEIKAGAKU. 59. 327-346 (1987)

井上贞子；井上康夫：SEIKAGAKU。

Daita NADANO: J.Biol.Chem.261. 11550-11557 (1986)

滩野大太：J.Biol.Chem.261。

Ken Kitajima;Yasuo Inoue;Sadako Inoue: THE JOURNAL OF BIOLOGICAL CHEMISTRY. 261. 5262-5269 (1986)

Ken Kitajima；Yasuo Inoue；Sadako Inoue：生物化学杂志。