Factors Influencing the Allergenicity and Adjuvanticity of Allergens

Stephan Deifl; Barbara Bohle

Disclosures

Immunotherapy. 2011;3(7):881-893. 

In This Article

Interaction With Non-TLR Pathogen Recognition Receptors

In addition to TLRs, DCs express various other PRRs including the C-type lectin receptors DC-specific ICAM-grabbing nonintegrin (DC-SIGN; CD209), dectin-1 and dectin-2. These non-TLR PRR recognize carbohydrate structures of microbiota and can modulate TLR signaling to tailor immune responses.[71] Most pathogens express carbohydrate structures (e.g., fucosylated glycans or mannose) on their surface, which can be compared with a 'sugar fingerprint'.[72] Of note, glycosylated allergens were also demonstrated to target C-type lectin receptors. The major peanut allergen Ara h 1 was shown to activate human DCs through DC-SIGNs to upregulate MHC class II and costimulatory molecules.[73] These DCs showed an increased ability to drive T-cell proliferation and induced IL-4- and IL-13-secreting Th2 cells two- to three-fold more than immature DCs. Recently, fucosylated structures on other common allergens such as Der p 2 in house dust mite or BG60 (Cyn dBG-60) in bermuda grass pollen were found to functionally interact with DC-SIGNs and its related receptor L-SIGN.[74] The mannose receptor, another C-type lectin receptor, was recently demonstrated to mediate the internalization of diverse allergens from mite (Der p 1 and Der p 2), dog (Can f 1), cockroach (Bla g 2) and peanut (Ara h 1) through their carbohydrate moieties.[75] Of note, silencing the mannose receptor expression on DCs reversed the Th2 polarization driven by exposure to Der p 1. In summary, glycosylated allergens can target C-type lectins in the innate immune system, which in turn may promote the induction of Th2-responses. This hypothesis suggests that both animal and plant carbohydrates may act as Th2 adjuvants.

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