We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein.
- Authors
Trompette, Aurelien; Divanovic, Senad; Visintin, Alberto; Blanchard, Carine; Hegde, Rashmi S; Madan, Rajat; Thorne, Peter S; Wills-Karp, Marsha; Gioannini, Theresa L; Weiss, Jerry P; Karp, Christopher L
- 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.
- Publication
Nature, 2009, Vol 457, Issue 7229, p585
- ISSN
1476-4687
- Publication type
Journal Article
- DOI
10.1038/nature07548