Journal article
Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein
Nature, Vol.457(7229), pp.585-588
2009
DOI: 10.1038/nature07548
PMCID: PMC2843411
PMID: 19060881
Abstract
Aeroallergy results from maladaptive immune responses to ubiquitous, otherwise innocuous environmental proteins. Although the proteins targeted by aeroallergic responses represent a tiny fraction of the airborne proteins humans are exposed to, allergenicity is a quite public phenomenon-the same proteins typically behave as aeroallergens across the human population. Why particular proteins tend to act as allergens in susceptible hosts is a fundamental mechanistic question that remains largely unanswered. The main house-dust-mite allergen, Der p 2, has structural homology with MD-2 (also known as LY96), the lipopolysaccharide (LPS)-binding component of the Toll-like receptor (TLR) 4 signalling complex. Here we show that Der p 2 also has functional homology, facilitating signalling through direct interactions with the TLR4 complex, and reconstituting LPS-driven TLR4 signalling in the absence of MD-2. Mirroring this, airway sensitization and challenge with Der p 2 led to experimental allergic asthma in wild type and MD-2-deficient, but not TLR4-deficient, mice. Our results indicate that Der p 2 tends to be targeted by adaptive immune responses because of its auto-adjuvant properties. The fact that other members of the MD-2-like lipid-binding family are allergens, and that most defined major allergens are thought to be lipid-binding proteins, suggests that intrinsic adjuvant activity by such proteins and their accompanying lipid cargo may have some generality as a mechanism underlying the phenomenon of allergenicity.
Details
- Title: Subtitle
- Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein
- Creators
- Senad Divanovic - University of CincinnatiAurelien Trompette - University of CincinnatiRashmi S. Hegde - University of CincinnatiRajat Madan - University of CincinnatiPeter S. Thorne - University of IowaMarsha Wills-Karp - University of CincinnatiTheresa L. Gioannini - University of IowaJerry P. Weiss - University of IowaChristopher L. Karp - University of CincinnatiAlberto Visintin - University of Massachusetts Medical SchoolCarine Blanchard - University of Cincinnati
- Resource Type
- Journal article
- Publication Details
- Nature, Vol.457(7229), pp.585-588
- DOI
- 10.1038/nature07548
- PMID
- 19060881
- PMCID
- PMC2843411
- NLM abbreviation
- Nature
- ISSN
- 1476-4687
- Copyright
- Copyright © 2008, Macmillan Publishers Limited. All rights reserved.
- Language
- English
- Date published
- 2009
- Academic Unit
- Civil and Environmental Engineering; Occupational and Environmental Health; Internal Medicine
- Record Identifier
- 9983557797702771
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