Mammal‐Derived Respiratory Lipocalin Allergens do not Exhibit Dendritic Cell‐Activating Capacity

Abstract

Most mammal-derived respiratory allergens belong to the lipocalin family of proteins. Determinants of their allergenic capacity are still unknown. Innate immune cells, in particular dendritic cells, have been shown to be involved in the allergenicity of some proteins. As recognition by dendritic cells is one of the few plausible mechanisms for the allergenicity of proteins, we wanted to investigate their role in the allergenicity of lipocalin allergens. Therefore, we first incubated human monocyte-derived dendritic cells with immunologically functional recombinant allergens mouse Mus m 1, dog Can f 1 and 2, cow Bos d 2, horse Equ c 1 and natural Bos d 2. Then, the surface marker expression and cytokine production of dendritic cells and their capacity to promote T cell proliferation and Th2 immune deviation in na€ ıve CD4 + T cells were examined in vitro. We found that near to endotoxin-free lipocalin allergens had no effect on the activation, allostimulatory capacity or cytokine production of dendritic cells. The dendritic cells could not induce immune deviation in na€ ıve CD4 + T cells. In contrast, lipopolysaccharide activated the dendritic cells efficiently. However, lipocalin allergens were not able to modify the lipopolysaccharide-induced responses. We conclude that an important group of mammal-derived respiratory allergens, lipocalins, appear not to be able to activate dendritic cells, a major component involved in the allergenicity of some proteins. It is conceivable that this incapacity of lipocalin allergens to arouse innate immunity may be associated with their poor capacity to induce a strong T cell response, verified in several studies.

Human CD4+ T Cell Responses to the Dog Major Allergen Can f 1 and Its Human Homologue Tear Lipocalin Resemble Each Other

“…In accordance with this conception, there are several reports indicating that in vitro T cell responses to an allergen do not correlate (or correlate very weakly) with the production of specific IgE in humans [23]–[25]. Therefore, poor T cell recognition, together with inefficient activation of the cells of innate immunity [76], also reported for several other allergens [77]–[79], appears as a likely immunological property of lipocalin allergens promoting their allergenicity since it is well documented that suboptimal T cell recognition of an antigen favors the development of Th2-type immune responses [43]–[53]. Nevertheless, good immunogenicity can be a characteristic for some other groups of allergens than lipocalins.…”

“…In particular, Can f 1 appears to be only marginally more potent to induce T cell responses than TL. As lipocalin allergens have also been shown to be weakly stimulatory to the cells of innate immunity [76], they may present themselves inert to the human immune system. When a protein with such characteristics encounters human atopic, Th2-biased immune environment, its subtle antigenicity may turn the fine balance of immunity for the favor of Th2 development.…”

Allergenic Can f 1 and its human homologue Lcn‐1 direct dendritic cells to induce divergent immune responses

“…Although most of the data shown in these reports are not directly comparable to our study, some are still contradictory. Virtanen and colleagues found that mammalian lipocalin allergens do not exhibit DC-activating capacity and found no differences in the CD4 + T cell responses to the two homologous lipocalins 38,39 while Preston et al . 40 found immunomodulatory activity of hard tick-derived lipocalins and Roth-Walter et al .…”

The Major Cow Milk Allergen Bos d 5 Manipulates T-Helper Cells Depending on Its Load with Siderophore-Bound Iron

“…Lipocalins share a common tertiary structure consisting of a β-barrel enclosing an internal ligand binding sites, but have very low sequence homology [25]. They are extracellular proteins whose expression is confirmed in bacteria, protoctists, plants, arthropods and chordates [26].…”