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

Trompette, A. et al. Nature 457, 585-589 (2009)

Speacker : Kuan-Ru Chen                                              Time: 13:00~14:00

Commentator: Dr. Chun-Keung Yu                                Place: Room 601

Abstract:

        Allergy is a symptomatic reaction to commonly innocuous environmental allergens, and is mainly mediated by T_H2 mediated air way inflammation. Dendritic cells have a key role in coupling innate and adaptive immune systems, and TLRs on DCs that participate in detecting PAMP and control of T cell activation. Previous studies indicated that TLR4 signalling has a crucial in allergic inflammatory response in the lung. Other studies also indicated that Der p 2, the main house dust mite allergen, has the structural homology to MD-2, a molecule conferring lipopolysaccharide responsiveness on TLR4. How aeroallergens have a propensity to generate maladaptive effector T-cell responses that remains unclear. Here this work first demonstrated that Der p 2 can reconstitute LPS-driven TLR4 signalling in the absence of MD-2, and enhancing TLR4 signalling in presence of MD-2. Further co-immunoprecipitation data showed that Der p 2 directly interacts with TLR4, CD14, MD2 and LPS. They also find the interactions of exogenously delivered Der p 2 facilitates LPS signalling in primary APCs. In vivo study, they find that airway sensitization and challenge with Der p 2 plus extremely low dosage LPS led to T_H2 inflammation in wild type and MD-2-deficient, but not TLR4-deficient mice. The Der p 2 mimics the function of MD-2 and can facilitate TLR4 signalling and airway T_H2 inflammation under the condition of low dosage of LPS. Many allergens, including Der p 2, are members of the MD2-like lipid-binding protein family and so such mimicry could also underlie the allergenicity of these allergens.

References：

1.     Herrick, C. A. & Bottomly, K. To respond or not to respond: T cells in allergic asthma. Nature Rev. Immunol. 3, 405–412 (2003).