Kao Daniela, Lux Anja, Schaffert Anja, Lang Roland, Altmann Friedrich, Nimmerjahn Falk
Chair of Genetics, Department of Biology, University of Erlangen-Nuremberg, Erlangen, Germany.
Chair of Microbiology and Infection Immunology, University Hospital Erlangen, Erlangen, Germany.
Eur J Immunol. 2017 Dec;47(12):2070-2079. doi: 10.1002/eji.201747208. Epub 2017 Aug 29.
Immunoglobulin G (IgG) glycosylation can modulate antibody effector functions. Depending on the precise composition of the sugar moiety attached to individual IgG glycovariants either pro- or anti-inflammatory effector pathways can be initiated via differential binding to type I or type II Fc-receptors. However, an in depth understanding of how individual IgG subclasses are glycosylated during the steady state and how their glycosylation pattern changes during vaccination is missing. To monitor IgG subclass glycosylation during the steady state and upon vaccination of mice with different T-cell dependent and independent antigens, tryptic digests of serum, and antigen-specific IgG preparations were analyzed by reversed phase-liquid chromatography-mass spectrometry. We show that there is a remarkable difference with respect to how individual IgG subclasses are glycosylated during the steady state. More importantly, upon T-cell dependent and independent vaccinations, individual antigen-specific IgG subclasses reacted differently with respect to changes in individual glycoforms, suggesting that the IgG subclass itself is a major determinant of restricting or allowing alterations in specific IgG glycovariants.
免疫球蛋白G（IgG）糖基化可调节抗体效应功能。根据附着于各个IgG糖变体的糖部分的确切组成，可通过与I型或II型Fc受体的差异结合启动促炎或抗炎效应途径。然而，目前尚缺乏对各个IgG亚类在稳态期间如何进行糖基化以及其糖基化模式在疫苗接种过程中如何变化的深入了解。为了监测小鼠在稳态期间以及用不同的T细胞依赖性和非依赖性抗原进行疫苗接种后的IgG亚类糖基化情况，通过反相液相色谱-质谱分析法分析了血清和抗原特异性IgG制剂的胰蛋白酶消化产物。我们发现，各个IgG亚类在稳态期间的糖基化方式存在显著差异。更重要的是，在T细胞依赖性和非依赖性疫苗接种后，各个抗原特异性IgG亚类在特定糖型变化方面反应不同，这表明IgG亚类本身是限制或允许特定IgG糖变体发生改变的主要决定因素。
