Factors Influencing the Allergenicity and Adjuvanticity of Allergens

Stephan Deifl; Barbara Bohle


Immunotherapy. 2011;3(7):881-893. 

In This Article

Enzymatic Activity

Several allergens with cysteine and serine protease activity have been cloned from house dust mites, including Der p 1, Der p 3, Der p 6 and Der p 9, and a significant body of evidence suggests that the enzymatic activity is important for their allergenicity. For example, the cystein protease Der p 1 has been shown to be able to cleave tight junctions, thereby facilitating allergen penetration at epithelial surfaces.[37] In addition, Der p 1 has been demonstrated to cleave various receptors on cells (i.e., the α-subunit of the IL-2 receptor [CD25] and the low-affinity IgE receptor [CD23]),[38] as well as the costimulatory molecule CD40 and C-type lectins expressed by DCs.[39] Moreover, Der p 1 can activate protease-activated receptor-2 in keratinocytes[40–42] and respiratory epithelial cells[43,44] and surfactant-associated proteins (SP-A and SP-D) in the lung.[45] All of these receptors are involved in the initiation or augmentation of Th2 responses. In in vivo experiments in mice, enzymatically active Der p 1 induced higher lung inflammatory responses as compared with enzymatically inactive Der p 1.[46] Furthermore, intranasal administration of Der p 1 and the homologous protease papain induced IL-25 (also known as IL-17E), which has been identified as one of the initiators of Th2 responses, and thymic stromal lymphopoietin, an IL-7-like cytokine that promotes Th2 differentiation.[47] In synergy, the enzymatic activity of allergens in house dust mite may promote Th2 responses, IgE synthesis and lung inflammation and explain why this allergen source is a very prevalent cause of allergic sensitization and often induces allergic asthma.[48,49] Of note, Der p 1 was demonstrated to directly activate basophils to produce IL-4, IL-5 and IL-13.[49] This observation was further confirmed by recent data on papain, which upregulated MHC class II and costimulatory molecules on murine basophils and induced Th2 responses and IgE production in mice.[50] Thus, enzymatic activity of allergens may alter typical type 2 effector cells to relevant APCs that promote the induction of Th2 responses.[51]

Together, the previously mentioned findings indicate that the enzymatic activity of allergens has an impact on the epithelial barrier function and various cell types involved in allergy. Apart from enzymatic activity of allergens, nonallergenic proteases in hazelnut and birch pollen were demonstrated to degrade human tear fluid and conjunctival cells.[52] Therefore, it was concluded that such enzymatic compounds in allergen sources may be the reason for seasonal conjunctivitis in individuals without proven allergy. However, it may also be speculated that the enzymatic activity of pollen may reduce the barrier function in other organs than the eye and thereby increase allergen uptake.