Repertoire of human natural anti-glycan immunoglobulins. Do we have auto-antibodies?
Repertoire of human natural anti-glycan immunoglobulins. Do we have auto-antibodies?
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DOI：
10.1016/j.bbagen.2012.02.005
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发表时间：
2012-09-01
影响因子：
3
通讯作者：
Huflejt, Margaret
中科院分区：
文献类型：
--
作者：
Bovin, Nicolai;Obukhova, Polina;Huflejt, Margaret
背景资料：使用聚糖阵列对供体抗体进行分析，证明存在能够结合>100种哺乳动物聚糖或其片段的抗体。例如，与Gal α 1-4Gal β 1-4GlcNAc（P-1）、Gal α 1-4Gal β 1-4Glc（P-k）、Gal β 1-3GlcNAc（Le（c））、4-O-SuGal β 1-4GlcNAc的相对高的结合。GalNAc α 1-3GalNAc（Fs）在所有受试个体中均存在。亲和分离使用半抗原特异性层析结合表位作图揭示了它们的糖表位。值得注意的是，大部分抗体能够识别较大聚糖的片段，例如糖脂的-Gal β 1-4Glc或Le（X）/Le（Y）抗原的Fuc α 1-3GlcNAc基序。它们的表位特异性在不同的健康个体之间没有变化。名义上，所有提到的免疫球蛋白都可以被归类为自身抗体。方法：在这项工作中，我们重新评估了先前发表的结果，并分析了新的数据，以解决为什么在健康个体中发现的自体抗体不会引起严重的自身免疫反应的问题。在所有的情况下，假定的“自身”抗体被发现结合短片段“减去”。而在整个天然链的情况下，相同片段的识别被完全消除。因此，尽管在打印的聚糖阵列上观察到许多形式上的阳性信号，但我们仍然不能在健康个体的血清中鉴定出能够以其天然存在形式结合碳水化合物链的真正的自身抗体。发现鉴定的天然抗聚糖抗体是特异性的，高滴度和群体保守的免疫球蛋白-所有这些都表明所研究的蛋白质的生物学作用尚不清楚。这篇文章是题为糖蛋白组学的特刊的一部分。(C)2012 Elsevier B. V.保留所有权利。
Background: Profiling of donor's antibodies using glycan arrays demonstrated presence of antibodies capable of binding to >100 mammalian glycans or their fragments. For example, relatively high binding to Gal alpha 1-4Gal beta 1-4GlcNAc (P-1), Gal alpha 1-4Gal beta 1-4Glc (P-k), Gal beta 1-3GlcNAc (Le(c)), 4-O-SuGal beta 1-4GlcNAc. and GalNAc alpha 1-3GalNAc (Fs) was found in all tested individuals. Affinity isolation using hapten-specific chromatography in combination with epitope mapping revealed their glycotopes. Notably, a significant part of the antibodies was capable of recognizing a fragment of larger glycans, for example, -Gal beta 1-4Glc of glycolipids, or Fuc alpha 1-3GlcNAc motif of Le(X)/Le(Y) antigens. Their epitope specificity did not vary between different healthy individuals. Nominally, all the mentioned immunoglobulins could be classified as auto-antibodies.Methods: In this work we re-evaluated results published earlier and analyzed new data to address the question why autologous antibodies found in healthy individuals do not cause severe auto-immune reactions.Results: In all cases the presumably "auto" antibodies were found to bind short fragments "subtracted" from larger glycans whereas recognition of the same fragment in the context of the whole natural chain was completely abolished. Thus, in spite of numerous formally positive signals observed on the printed glycan array, we are yet unable to identify in blood serum of healthy individuals true auto-antibodies capable of binding carbohydrate chains in their naturally occurring form.General significance: The identified natural anti-glycan antibodies were found to be specific, high-titer and population conservative immunoglobulins - all of this suggesting as yet unknown biological role(s) of the studied proteins. This article is part of a Special Issue entitled Glycoproteomics. (C) 2012 Elsevier B.V. All rights reserved.