Anti-carbohydrate antibodies of normal sera: Findings, surprises and challenges

Anti-carbohydrate antibodies of normal sera: Findings, surprises and challenges
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DOI:
10.1016/j.molimm.2009.06.010
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发表时间:
2009-09-01
影响因子:
3.6
通讯作者:
Bovin, Nicolai
Bovin, Nicolai
中科院分区:
医学3区
文献类型:
--
作者:
Huflejt, Margaret E.;Vuskovic, Marko;Bovin, Nicolai

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我们使用微芯片格式的聚糖阵列来表征 106 名健康捐赠者血清中抗体 (Ab) 的个体碳水化合物识别模式。聚糖库包括血型抗原和其他最常见的末端寡糖及其哺乳动物N-和O-连接糖蛋白和糖脂的核心、肿瘤相关糖抗原以及细菌/致病多糖和脂多糖的常见成分,总共205个聚糖。血清抗体与至少 50 个正常人类糖基序相互作用。除了预期的血型、异种(异嗜)和感染相关的结合活性外,我们还观察到了许多新的和意想不到的特征。令人惊讶的是,发现了与血型 P-1 和 P-k 三糖以及 H(2 型)三糖的抗体结合力相对较高。已观察到针对 Gal beta 1-3GlcNAc (Le(C)) 相关聚糖(尤其是 3'-O-Su-Le(C))和 4'-O-硫酸化乳糖胺的新颖且非常高的结合活性。相对较高且均匀的 Ab 与 GalNAc α 1-3Gal 二糖的结合表明与岩藻糖基化血型 A GalNAc α 1-3(Fuc α 1-2)Gal 抗原不存在相关性,这与众所周知的 Gal α 1-3Gal 和真正的岩藻糖基化血型 B Gal α 1-3(Fuc α 1-2)Gal 抗原之间的关系类似。显示与 Gal α 1 -3Gal beta 1-4GlcNAc 异种抗原的结合强度相当适中。发现针对寡唾液酸、唾液酸寡糖(SiaT(n) 除外)、2 型骨架聚糖(如 Le(y))和双触角 N 链及其截短形式(即没有末端 Sia、SiaGal 和 SiaGalGlcNAc 基序)的 Ab 结合不存在或非常低。我们还发现 Ab 能够将糖脂 (-Gal beta 1 -4Glc) 和糖蛋白 (-GalNAc alpha) 典型的短内核识别为较大聚糖的片段。 (C) 2009 Elsevier Ltd. 保留所有权利。
We have used microchip format glycan array to characterize the individual carbohydrate recognition patterns by antibodies (Ab) in sera of 106 healthy donors. The glycan library included blood group antigens and other most frequent terminal oligosaccharides and their cores of mammalian N- and O-linked glycoproteins and glycolipids, tumor-associated carbohydrate antigens, and common components of bacterial/pathogenic polysaccharides and lipopolysaccharides, totally 205 glycans. The serum Ab interacted with at least 50 normal human glyco-motifs. Apart from expected blood group-, xeno- (heterophil) and infection-related binding activities, we observed a number of new and unexpected features. The surprising, relatively high antibody binding was found to the blood group P-1 and P-k trisaccharides and H(type 2) trisaccharide. Novel and very high binding activities have been observed towards Gal beta 1-3GlcNAc (Le(C)) related glycans, especially 3'-O-Su-Le(C), and towards 4'-O-sulfated lactosamine. Relatively high and uniform Ab binding to GalNAc alpha 1-3Gal disaccharide demonstrated absence of correlation with fucosylated blood group A GalNAc alpha 1-3(Fuc alpha 1-2)Gal antigen-similarly to well known relationship between Gal alpha 1-3Gal and true, fucosylated blood group B Gal alpha 1-3(Fuc alpha 1-2)Ga1 antigen. The binding intensity to Gal alpha 1 -3Gal beta 1-4GlcNAc xenoantigen was shown to be rather modest. Absence or very low Ab binding was found against oligosialic acid, sialooligosaccharides except SiaT(n), type 2 backbone glycans such as Le(y), and biantennary N-chain as well as its truncated forms, i.e. without terminal Sia, SiaGal, and SiaGalGlcNAc motifs. We have also found that Ab are capable of recognizing the short inner core typical for glycolipids (-Gal beta 1 -4Glc) and glycoproteins (-GalNAc alpha) as a fragment of bigger glycams. (C) 2009 Elsevier Ltd. All rights reserved.