Factors Influencing the Allergenicity and Adjuvanticity of Allergens

Stephan Deifl; Barbara Bohle

Disclosures

Immunotherapy. 2011;3(7):881-893. 

In This Article

Interaction With TLRs

The tertiary structure of group 2 allergens in house dust mites (e.g., Der p 2 and Der f 2) is homologous to MD-2. MD-2 belongs to the MD-2-related lipid-recognition (ML) domain lipid-binding family and is the LPS-binding component of the TLR4 signaling complex essential for the recognition of LPS.[68] Indeed, Der f 2 binds LPS with a nanomolar affinity in a manner similar to the binding by MD-2.[50] Der p 2 also binds LPS although with lower affinity than MD-2.[69] Still, Der p 2 was demonstrated to facilitate signaling through direct interactions with the TLR4 complex[70] and could reconstitute LPS-driven TLR4-signaling even in the absence of MD-2. Mirroring these properties, airway sensitization and challenge with Der p 2 led to experimental allergic asthma in wild-type and MD-2-deficient mice, but not TLR4-deficient mice. The fact that also several other allergens are members of the MD-2-like lipid-binding family may suggest that mimicking MD-2 may foster their capacity to activate innate immune responses.

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