Factors Influencing the Allergenicity and Adjuvanticity of Allergens

Stephan Deifl; Barbara Bohle

Disclosures

Immunotherapy. 2011;3(7):881-893. 

In This Article

Future Perspective

Some biochemical features (e.g., enzymatic activity or lipid-binding capacity) and the interaction with elements of the innate immune system were suggested to underlie the phenomenon of allergenicity (Figure 2). However, it is difficult to judge their physiological relevance in humans and as a consequence we are still not able to fully answer the question of why particular proteins tend to act as allergens in susceptible individuals whereas others do not. Certainly, some of the mentioned characteristics may explain why certain proteins are major allergens. Nevertheless, many of the proposed features of allergenicity are shared by minor allergens and nonallergenic proteins. More importantly, studies contradicting some concepts of allergenicity have been published. One example is the finding that a trimeric form of the birch pollen allergen is less allergenic than native Bet v 1,[117] which rebuts the concept of dimerization/oligomerization as important factor for allergenicity. Furthermore, the fact that many proteases are no allergens contradicts the concept of enzymatic activity as an important factor for allergenicity. Therefore, apart from special characteristics of individual major allergens, other aspects (e.g., their abundance and stability in the environment, the role of nonallergenic components in allergen sources as well as the route of exposure) need to be taken into account to explain what makes a protein allergenic.

Figure 2.

Characteristics of allergens associated with their capacity to induce IgE production. Enzymatic activity of allergens breaks barrier function and activates cells of the innate and adaptive immune response. Some allergens can directly interact with TLR or indirectly via bound lipids or lipopolysaccharide. Carbohydrate determinants on allergens activate C-type lectins (e.g., DC-specific ICAM-grabbing nonintegrin). Dimers of allergens promote the activation of basophils that release mediators and IL-4.
Ba: Basophil; DC: Dendritic cell; LPS: Lipopolysaccharide; T: Naive CD4+ T cell; TLR: Toll-like receptor.

Allergy is a multifactorial disorder of the immune system and in addition to genetic predisposition special characteristics of allergens certainly contribute to allergy development. Therefore, nailing down special features of allergenicity definitely helps us to understand how allergen-specific IgE responses evolve. In addition, these insights will contribute to the improvement of therapeutic interventions for allergic disorders. Recent studies have supported the concept that adding adjuvanticity to allergens increases their immunomodulatory capacity and thereby may improve their therapeutic efficacy (Figure 3). In particular, recombinant fusion proteins of allergens and bacterial proteins that represent danger signals for the immune system have revealed promising results in mouse models of allergy. Furthermore, these vaccine candidates have advantages regarding production, standardization and immunological consistence and should now be tested in humans in order to prove their efficacy to cure allergic disorders.

Figure 3.

Creating intrinsic adjuvanticity for allergens. Allergens can be genetically fused with TLR ligands; the resulting fusion protein activates DC to promote the differentiation of allergen-specific Th1 and Treg cells.
DC: Dendritic cell; TLR: Toll-like receptor.

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