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

Aurelien Trompette, Senad Divanovic, Alberto Visintin, Carine Blanchard, Rashmi S. Hegde, Rajat Madan, Peter S. Thorne, Marsha Wills-Karp, Theresa L. Gioannini, Jerry P. Weiss, Christopher L. Karp

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)585-588
Number of pages4
JournalNature
Volume457
Issue number7229
DOIs
StatePublished - Jan 29 2009
Externally publishedYes

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Toll-Like Receptors
Allergens
Proteins
Lipids
Lipopolysaccharides
Dermatophagoides Antigens
Toll-Like Receptor 4
Adaptive Immunity
Carrier Proteins
Asthma
Dermatophagoides pteronyssinus antigen p 2
Population

ASJC Scopus subject areas

  • General

Cite this

Trompette, A., Divanovic, S., Visintin, A., Blanchard, C., Hegde, R. S., Madan, R., ... Karp, C. L. (2009). Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein. Nature, 457(7229), 585-588. https://doi.org/10.1038/nature07548

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

In: Nature, Vol. 457, No. 7229, 29.01.2009, p. 585-588.

Research output: Contribution to journalArticle

Trompette, A, Divanovic, S, Visintin, A, Blanchard, C, Hegde, RS, Madan, R, Thorne, PS, Wills-Karp, M, Gioannini, TL, Weiss, JP & Karp, CL 2009, 'Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein', Nature, vol. 457, no. 7229, pp. 585-588. https://doi.org/10.1038/nature07548
Trompette A, Divanovic S, Visintin A, Blanchard C, Hegde RS, Madan R et al. Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein. Nature. 2009 Jan 29;457(7229):585-588. https://doi.org/10.1038/nature07548
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. / Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein. In: Nature. 2009 ; Vol. 457, No. 7229. pp. 585-588.
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