Adaptive immune activation: glycosylation does matter

Wolfert, Margreet A.; Boons, Geert‐Jan

doi:10.1038/nchembio.1403

Cited by 271 publications

(230 citation statements)

References 110 publications

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“…N-and O-linked glycans carried by cell surface glycoproteins and glycolipids are involved in different physiological or pathological processes, such as host defense, immunological and inflammatory responses, tissue homeostasis or cancers 6,7 . In particular, carbohydrates participate to multiple mechanisms of cellular regulation including intracellular trafficking, endocytosis, folding and proteolysis, cell communication, regulation of signaling pathways, as well as cell differentiation, adhesion and growth 8,9 .…”

Section: Introductionmentioning

confidence: 99%

Glycosylation Changes Triggered by the Differentiation of Monocytic THP-1 Cell Line into Macrophages

et al. 2016

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The human acute monocytic leukemia cell line THP-1 is widely used as an in vitro phagocytic cell model because it exhibits several immune properties similar to native monocyte-derived macrophages. In this study, we investigated the alteration of N- and O-linked glycans as well as glycosphingolipids, during THP-1 differentiation, combining mass spectrometry, flow cytometry, and quantitative real-time PCR. Mass spectrometry revealed that macrophage differentiation led to a marked upregulation of expression of GM3 ganglioside as well as an increase in complex-type structures, particularly triantennary glycans, occurring at the expense of high-mannose N-glycans. Moreover, we observed a slight decrease in the proportion of multifucosylated N-glycans and α2,6-sialylation. The uncovered changes in glycosylation correlated with variations of gene expression of relevant glycosyltransferases and glycosidases including sialyltransferases, β-N-acetylglucosaminyltransferases, fucosyltransferases, and neuraminidase. Furthermore, using flow cytometry and antibodies directed against glycan structures, we confirmed that the alteration of glycosylation occurs at the cell surface of THP-1 macrophage-like cells. Altogether, we established that macrophagic maturation of THP-1 induces dramatic modifications of the surface glycosylation pattern that may result in differential interaction of monocytic and macrophagic THP-1 with immune or bacterial lectins.

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Section: Introductionmentioning

confidence: 99%

Glycosylation Changes Triggered by the Differentiation of Monocytic THP-1 Cell Line into Macrophages

et al. 2016

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“…Manipulation of protein glycosylation has been recognized as a strategy to promote antigen internalization and antigen presentation via MHC class I and class II molecules promoting cellular and humoral immune responses (44). Targeting the mannose receptor, a C-type lectin, showed that mannosylation provided an efficient strategy to improve antigen uptake, processing, and presentation.…”

mentioning

confidence: 99%

Modification of Asparagine-Linked Glycan Density for the Design of Hepatitis B Virus Virus-Like Particles with Enhanced Immunogenicity

Hyakumura

Walsh

Thaysen‐Andersen

et al. 2015

J Virol

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The small envelope proteins (HBsAgS) derived from hepatitis B virus (HBV) represent the antigenic components of the HBV vaccine and are platforms for the delivery of foreign antigenic sequences. To investigate structure-immunogenicity relationships for the design of improved immunization vectors, we have generated biochemically modified virus-like particles (VLPs) exhibiting glycoengineered HBsAgS. For the generation of hypoglycosylated VLPs, the wild-type (WT) HBsAgS N146 glycosylation site was converted to N146Q; for constructing hyperglycosylated VLPs, potential glycosylation sites were introduced in the HBsAgS external loop region at positions T116 and G130 in addition to the WT site. The introduced T116N and G130N sites were utilized as glycosylation anchors resulting in the formation of hyperglycosylated VLPs. Mass spectroscopic analyses showed that the hy-

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“…that can promote uptake of antigens, such as dendritic cells (45)(46)(47)(48)(49). It is known that HA from viruses that are adapted to circulate in humans contains more glycosylation sites in the globular head domain compared to avian HA (44).…”

Section: Discussionmentioning

confidence: 99%

Avian and Human Seasonal Influenza Hemagglutinin Proteins Elicit CD4 T Cell Responses That Are Comparable in Epitope Abundance and Diversity

DiPiazza

Richards

Poulton

et al. 2017

Clin Vaccine Immunol

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Avian influenza viruses remain a significant concern due to their pandemic potential. Vaccine trials have suggested that humans respond poorly to avian influenza vaccines relative to seasonal vaccines. It is important to understand, first, if there is a general deficiency in the ability of avian hemagglutinin (HA) proteins to generate immune responses and, if so, what underlies this defect. This question is of particular interest because it has been suggested that in humans, the poor immunogenicity of H7 vaccines may be due to a paucity of CD4 T cell epitopes. Because of the generally high levels of cross-reactive CD4 T cells in humans, it is not possible to compare the inherent immunogenicities of avian and seasonal HA proteins in an unbiased manner. Here, we empirically examine the epitope diversity and abundance of CD4 T cells elicited by seasonal and avian HA proteins. HLA-DR1 and HLA-DR4 transgenic mice were vaccinated with purified HA proteins, and CD4 T cells to specific epitopes were identified and quantified. These studies revealed that the diversity and abundance of CD4 T cells specific for HA do not segregate on the basis of whether the HA was derived from human seasonal or avian influenza viruses. Therefore, we conclude that failure in responses to avian vaccines in humans is likely due to a lack of cross-reactive CD4 T cell memory perhaps coupled with competition with or suppression of naive, HA-specific CD4 T cells by memory CD4 T cells specific for more highly conserved proteins.

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Adaptive immune activation: glycosylation does matter

Cited by 271 publications

References 110 publications

Glycosylation Changes Triggered by the Differentiation of Monocytic THP-1 Cell Line into Macrophages

Glycosylation Changes Triggered by the Differentiation of Monocytic THP-1 Cell Line into Macrophages

Modification of Asparagine-Linked Glycan Density for the Design of Hepatitis B Virus Virus-Like Particles with Enhanced Immunogenicity

Avian and Human Seasonal Influenza Hemagglutinin Proteins Elicit CD4 T Cell Responses That Are Comparable in Epitope Abundance and Diversity

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