Recognition of the major cat allergen Fel d 1 through the cysteine-rich domain of the mannose receptor determines its allergenicity

Emara, Mohamed; Royer, Pierre Joseph; Abbas, Zaigham; Sewell, Herb F.; Gebriel Mohamed, Gihan; Singh, Sonali; Peel, Samantha; Fox, Jane; Shakib, Farouk; Martinez-Pomares, Luisa; Ghaemmaghami, Amir M.

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.Wehave 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 MRplays 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. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

Citation

Emara, M., Royer, P. J., Abbas, Z., Sewell, H. F., Gebriel Mohamed, G., Singh, S., Peel, S., Fox, J., Shakib, F., Martinez-Pomares, L., & Ghaemmaghami, A. M. (2011). Recognition of the major cat allergen Fel d 1 through the cysteine-rich domain of the mannose receptor determines its allergenicity. Journal of Biological Chemistry, 286(15), 13033-13040. https://doi.org/10.1074/jbc.M111.220657

• Journal Article Type: Article
• Publication Date: Apr 15, 2011
• Deposit Date: Jan 3, 2023
• Publicly Available Date: Jan 27, 2023
• Journal: Journal of Biological Chemistry
• Print ISSN: 0021-9258
• Electronic ISSN: 1083-351X
• Publisher: American Society for Biochemistry and Molecular Biology
• Peer Reviewed: Peer Reviewed
• Volume: 286
• Issue: 15
• Pages: 13033-13040
• DOI: https://doi.org/10.1074/jbc.M111.220657
• Public URL: https://nottingham-repository.worktribe.com/output/3097534
• Publisher URL: https://www.jbc.org/article/S0021-9258(20)51684-0/fulltext#seccestitle10