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

1978年，Inoue和Iwasaki在虹鳟鱼卵中发现了一类新的唾液酸糖蛋白。这些糖蛋白最显著的特征是存在寡（聚）唾液酸链，我们将其命名为聚唾液酸糖蛋白（PSGP）。我们已经表明，PSGP是一个无处不在的组成部分，所有物种的鲑鱼检查的鸡蛋。由于<alpha>B群脑膜炎球菌（脑膜炎奈瑟氏菌）中存在的N-乙酰神经氨酸（NeuAc）结构的-2，8-连接均聚物是致病性的，因此进行本研究以引发针对聚唾液酸的抗体。<alpha>已知2，8-连接的聚（NeuAc）在包括人在内的各种动物中是极差的免疫原。虹鳟鱼卵PSGP仅含有N-羟乙酰神经氨酸（NeuGc），因此我们用它作为免疫原<alpha>在兔和BALB/c小鼠中产生-2，8-连接的聚（NeuGc）抗体。我们继续进行了16个月的抗原注射，但在所有动物的血清中均检测到NP抗体。 ...更多信息 观察到的免疫原性差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，使得免疫可能被免疫耐受抑制。最近，我们成功地诱导了抗虹鳟鱼PSGP的抗血清。我们还检查<alph>了2，8-连接的聚（NeuGc）链对独特的抗血清（“H-46”）的免疫反应性，所述抗血清由J. B. Robbins（N.I.H.）使用福尔马林处理的B群脑膜炎球菌作为免疫原免疫马，服用7年后。已证明含有多克隆IgM抗体的H.46抗血清不形成针对<alpha>-2，8-连接的聚（NeuGc）的免疫荧光素条带。因此，H.46与<alpha>-2，8-连接的poly（NeuAc）特异性结合，只能作为poly（NeuAc）的探针。在这方面，我们的结果对鸡，虽然初步的，可以提供针对聚（NeuGc）的特异性抗体，它可能被用作诊断工具，用于检测聚（NeuGc）在各种动物组织。少

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