title: Recognition of the major cat allergen Fel d 1 through the cysteine-rich domain of the mannose receptor determines its allergenicity.
abstract: Dendritic cells are professional antigen-presenting cells that are specialized in antigen uptake and presentation. Allergy to cat has increased substantially in recent years and has been shown to be positively associated with asthma. We have recently shown that the mannose receptor (MR), a C-type lectin expressed by dendritic cells, recognizes various glycoallergens from diverse sources and is involved in promoting allergic responses to a major house dust mite allergen in vitro. Here we investigated the potential role of MR in allergic responses to Fel d 1, a major cat allergen. Fel d 1 binding to MR was confirmed by ELISA. Using blocking, gene silencing (siRNA) experiments, and MR knock-out (MR(-/-)) cells, we have demonstrated that MR plays a major role in internalization of Fel d 1 by human and mouse antigen-presenting cells. Intriguingly, unlike other glycoallergens, recognition of Fel d 1 by MR is mediated by the cysteine-rich domain, which correlates with the presence of sulfated carbohydrates in natural Fel d 1. WT and MR(-/-) mice were used to study the role of MR in allergic sensitization to Fel d 1 in vivo. MR(-/-) mice sensitized with cat dander extract and Fel d 1 produced significantly lower levels of total IgE, Fel d 1-specific-IgE and IgG1, the hallmarks of allergic response, compared with WT mice. Our data show for the first time that Fel d 1 is a novel ligand of the cysteine-rich domain of MR and that MR is likely to play a pivotal role in allergic sensitization to airborne allergens in vivo.
authors.affiliation: School of Molecular Medical Sciences, Queen’s Medical Centre, The University of Nottingham, Nottingham NG7 2UH, United Kingdom.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Emara
authors.forename: Pierre-Joseph
authors.initials: PJ
authors.lastname: Royer
authors.forename: Zaigham
authors.initials: Z
authors.lastname: Abbas
authors.forename: Herb F
authors.initials: HF
authors.lastname: Sewell
authors.forename: Gihan Gebriel
authors.initials: GG
authors.lastname: Mohamed
authors.forename: Sonali
authors.initials: S
authors.lastname: Singh
authors.forename: Samantha
authors.initials: S
authors.lastname: Peel
authors.forename: Jane
authors.initials: J
authors.lastname: Fox
authors.forename: Farouk
authors.initials: F
authors.lastname: Shakib
authors.forename: Luisa
authors.initials: L
authors.lastname: Martinez-Pomares
authors.forename: Amir M
authors.initials: AM
authors.lastname: Ghaemmaghami
mesh_terms: D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002415:Cats; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D020868:Gene Silencing; D006023:Glycoproteins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D007074:Immunoglobulin G; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D007073:Immunoglobulin E; C059296:Fel d 1 protein, Felis domesticus