A single glycan on IgE is indispensable for initiation of anaphylaxis

Shade, Kai-Ting C.; Platzer, Barbara; Washburn, Nathaniel; Mani, V.; Bartsch, Yannic C.; Conroy, Michelle; Pagan, Jose D.; Bosques, Carlos J.; Mempel, Thorsten R.; Fiebiger, Edda; Anthony, Robert M.

doi:10.1084/jem.20142182

Cited by 110 publications

(134 citation statements)

References 29 publications

(48 reference statements)

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“…This suggests that the glycosylation at Asn402 is important, and that high mannose-type glycans at this site may play a role in complement activation. This was also observed in human IgE, where the single high mannose containing Asn394 was required for IgE binding to FcɛR [67]. The Asn402 glycosylation of pentameric and hexameric IgM appears highly conserved, even at the individual glycan compositional level (R 2 = 0.9953, Supplementary S5).…”

Section: High Mannose Containing Asn402mentioning

confidence: 60%

“…Although some of these glycans could be classified as being part of the bi-antennary type, bisecting lactosamine and LacdiNAc epitopes are all unique structural features that differ from the regular bi-antennary glycans. While diagnostic tandem MS fragment ions might be able to distinguish the presence of some of these structures (e.g., m/z 407 1+ , HexNAc 2 ; m/z 698 1+ , NeuAcHexNAc 2 from LacdiNAc containing glycans; Y-ion specific for HexNAc 2 Hex 1 HexNAc 1 of bisecting glycans [67]), isobaric glycopeptides with the same composition but different structures are not resolved well enough by the capillary C18 column to distinguish them.…”

Section: Comparison Of Site-specific Glycosylation Of Pentameric and mentioning

confidence: 99%

“…Asn402 is located on the C H 3 domain of the Ig mu heavy chain, and is described to be homologous to the single IgG N-glycosylation site (Asn297) [40,71], and to the single high mannose site amongst the seven N-glycosylation sites of human IgE (Asn394) [67]. These three sites have all been demonstrated to be important for antibody-receptor binding; IgG to FcɣRIII [24], IgM to complement [40], and IgE to FcɛRI [67].…”

Section: High Mannose Containing Asn402mentioning

confidence: 99%

“…These three sites have all been demonstrated to be important for antibody-receptor binding; IgG to FcɣRIII [24], IgM to complement [40], and IgE to FcɛRI [67]. For mouse IgM, it was also found that upon mutagenesis of the nearby amino acid Ser406Asn resulted in abnormal Asn402 glycosylation as determined by electrophoretic migration, and resulted in a decrease in the ability of IgM to activate complement [4].…”

Section: High Mannose Containing Asn402mentioning

confidence: 99%

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Site-SpecificN-Glycosylation of Recombinant Pentameric and Hexameric Human IgM

Moh

Lin

Thaysen‐Andersen

et al. 2016

J. Am. Soc. Mass Spectrom.

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Abstract. Glycosylation is known to play an important role in IgG antibody structure and function. Polymeric IgM, the largest known antibody in humans, displays five potential N-glycosylation sites on each heavy chain monomer. IgM can exist as a pentamer with a connecting singly N-glycosylated J-chain (with a total of 51 glycosylation sites) or as a hexamer (60 glycosylation sites). In this study, the N-glycosylation of recombinant pentameric and hexameric IgM produced by the same human cell type and culture conditions was site-specifically profiled by RP-LC-CID/ETD-MS/ MS using HILIC-enriched tryptic and GluC glycopeptides. The occupancy of all putative N-glycosylation sites on the pentameric and hexameric IgM were able to be determined. Distinct glycosylation differences were observed between each of the five N-linked sites on the IgM heavy chains. While Asn171, Asn332, and Asn395 all had predominantly complex type glycans, differences in glycan branching and sialylation were observed between the sites. Asn563, a high mannose-rich glycosylation site that locates in the center of the IgM polymer, was only approximately 60% occupied in both the pentameric and hexameric IgM forms, with a difference in relative abundance of the glycan structures between the pentamer and hexamer. This study highlights the information obtained by characterization of the site-heterogeneity of a highly glycosylated protein of high molecular mass with quaternary structure, revealing differences that would not be seen by global glycan or deglycosylated peptide profiling.

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Section: High Mannose Containing Asn402mentioning

confidence: 60%

Section: Comparison Of Site-specific Glycosylation Of Pentameric and mentioning

confidence: 99%

Section: High Mannose Containing Asn402mentioning

confidence: 99%

Section: High Mannose Containing Asn402mentioning

confidence: 99%

See 2 more Smart Citations

Site-SpecificN-Glycosylation of Recombinant Pentameric and Hexameric Human IgM

Moh

Lin

Thaysen‐Andersen

et al. 2016

J. Am. Soc. Mass Spectrom.

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“…Importantly, it has been suggested that glycan may be crucial in cockroach allergen-induced allergic asthma. For example, surface epitopes mapped from a murine monoclonal antibody against Bla g 2, 4C3, was found to contain a carbohydrate moiety (54, 55) and the prevention of Bla g 2 glycosylation by nucleotide point mutation significantly reduces IgE binding, Th2 cytokine IL-13 production, and increased IL-10 (32, 44). Our recent studies have also demonstrated that Bla g 2 specific IgE from patients with cockroach allergy may be, at least partially, due to glycans (unpublished data).…”

Section: Introductionmentioning

confidence: 99%

Cockroach allergen exposure and risk of asthma

Danh

Zhao

Gao

2016

Allergy

121

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Cockroach sensitization is an important risk factor for the development of asthma. However, its underlying immune mechanisms and the genetic etiology for differences in allergic responses remain unclear. Cockroach allergens identification and their expression as biologically active recombinant proteins has provided a basis for studying the mechanisms regarding cockroach allergens induced allergic sensitization and asthma. Glycans in allergens may play a crucial role in the immunogenicity of allergic diseases. Protease-activated receptor (PAR)-2, Toll-like receptor (TLR), and C-type lectin receptors have been suggested to be important for the penetration of cockroach allergens through epithelial cells to mediate allergen uptake, dendritic cell maturation, antigen presenting cell (APC) function in T cell polarization, and cytokine production. Environmental pollutants, which often co-exist with the allergen, could synergistically elicit allergic inflammation, and aryl hydrocarbon receptor (AhR) activation and signaling may serve as a link between these two elements. Genetic factors may also play an important role in conferring the susceptibility to cockroach sensitization. Several genes have been associated with cockroach sensitization and asthma-related phenotypes. In this review, we will discuss the epidemiological evidence for cockroach allergen-induced asthma, cockroach allergens, the mechanisms regarding cockroach allergens induced innate immune responses, and the genetic basis for cockroach sensitization.

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Cell surface expression of human RP105 depends on N‐glycosylation of MD‐1

et al. 2022

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For its cell surface expression, radioprotective 105 (RP105)an orphan Toll-like receptormust form a complex with a soluble glycoprotein called myeloid differentiation 1 (MD-1). The number of RP105-negative cells is significantly increased in patients with systemic lupus erythematosus (SLE); however, to elucidate the mechanism underlying this increase, how RP105 is expressed on the cell surface depending on MD-1 should be investigated. We demonstrated that RP105 exhibits two forms depending on MD-1 and its two N-glycosylation sites, N96 and N156. Cell surface expression of RP105 decreased in the presence of mutant MD-1 (N96Q/N156Q). Nonglycosylated MD-1 decreased the de novo cell surface expression of RP105 but not preexpressed RP105. Thus, the N-glycans of MD-1 may represent targets for SLE therapy.

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A single glycan on IgE is indispensable for initiation of anaphylaxis

Abstract: Shade et al. demonstrate the requirement for IgE glycosylation in allergic reactions.

Cited by 110 publications

References 29 publications

Site-SpecificN-Glycosylation of Recombinant Pentameric and Hexameric Human IgM

Site-SpecificN-Glycosylation of Recombinant Pentameric and Hexameric Human IgM

Cockroach allergen exposure and risk of asthma

Cell surface expression of human RP105 depends on N‐glycosylation of MD‐1

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