Details

Autor(en) / Beteiligte

• Karp, Christopher L
• 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

Titel

Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein

Ist Teil von

• Nature, 2009-01, Vol.457 (7229), p.585-588

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2009

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.