Factors Influencing the Allergenicity and Adjuvanticity of Allergens

Stephan Deifl; Barbara Bohle

Disclosures

Immunotherapy. 2011;3(7):881-893. 

In This Article

Binding of Lipids

Many major allergens have been found to be lipid-binding proteins, suggesting that the accompanying lipid cargo may contribute to their allergenicity. For example, the house dust mite allergens Der f 2 and Der p 2 bind lipopolysaccharide (LPS) from bacteria because they show structural similarity with LPS-binding protein.[53] Der p 7, another house dust mite allergen, does not bind LPS but binds the bacterial lipopeptide polymyxin B with weak affinity.[54] Also, the primary amino acid structure of the group 14 allergens in house dust mite clearly defines them as lipid-binding proteins.[55] Other respiratory allergens with lipid binding capacity are Par j 1 and Par j 2, two major allergens in Parietaria judaica, which preferentially bind monoacylated negative lipids.[56] The group of nonspecific lipid transfer proteins (nsLTP), which are major allergens in Rosaceae fruits in birch-free areas in Southern Europe, were named after their capacity to possess a broad lipid-binding specificity closely related to their 3D structure.[57] Finally, the 3D structure of the major birch pollen allergen Bet v 1 revealed a solvent-accessible cavity that traverses the core of the molecule.[58] In this cavity, Bet v 1 can bind ligands such as fatty acids, flavonoids and cytokinins. By employing the fluorescent sterol dehydroergosterol, first qualitative and quantitative data on the ligand-binding properties of a major allergen have been obtained.[59]

In summary, lipid binding can be noted as a very common characteristic of many important groups of allergens. Bacterial lipopeptides bound to allergens may promote Th2 immunity through activation of TLR pathways. In fact, various bacterial and mycobacterial lipopeptides can induce the release of cytokines through interactions with TLR2, which cooperates with TLR1 or TLR6. As shown for peptidoglycan and the synthetic ligand Pam3Cys, stimulation of TLR2 in the presence of allergen enhances Th2 responses in mice.[60,61] LPS from Gram-negative bacteria is recognized by TLR4 and represents a strong danger signal for the human immune system. In general, high amounts of LPS foster the induction of Th1-like responses, whereas low amounts support the induction of Th2-responses.[62] Recently, a critical involvement of TLR4 signaling in the induction of Th2 responses to inhaled antigens was reported.[63]

Interestingly, it has been demonstrated that in a humid milieu such as mucosal surfaces of the human body pollen grains release pollen-associated lipid mediators in addition to allergens.[64] Pollen-derived E(1) phytoprostanes were found to modulate the function of human DC in a manner that favors the polarization of Th2 cells.[65–67] Alhough it has not been investigated in detail yet, it may be speculated that pollen allergens with lipid-binding capacity may also bind pollen-associated lipid mediators, which may then contribute to their allergenicity.

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