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Immune responses to inhalant Mammalian allergens.

ABSTRACT: In Europe and the USA, at least one person in four is exposed every day to inhalant allergens of mammalian origin, a considerable number is regularly exposed for professional reasons and almost everyone is occasionally exposed to inhalant allergens from pets or domestic animals. The production of IgE to these inhalant allergens, often complicated by asthma and rhinitis, defines the atopic status. However, the immune response to these allergens largely imprints the cellular immune compartment and also drives non-IgE humoral immune responses in the allergic and non-allergic population. During the recent years, it has become clear that IgE antibodies recognize mammalian allergens that belong to three protein or glycoprotein families: the secretoglobins, the lipocalins, and the serum albumins. In this article, we review the humoral and cellular immune responses to the major members of these families and try to define common characteristics and also distinctive features.

SUBMITTER: Hentges F

PROVIDER: S-EPMC4033121 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Immune responses to inhalant Mammalian allergens.

Hentges François F Léonard Cathy C Arumugam Karthik K Hilger Christiane C

Frontiers in immunology 20140521

In Europe and the USA, at least one person in four is exposed every day to inhalant allergens of mammalian origin, a considerable number is regularly exposed for professional reasons and almost everyone is occasionally exposed to inhalant allergens from pets or domestic animals. The production of IgE to these inhalant allergens, often complicated by asthma and rhinitis, defines the atopic status. However, the immune response to these allergens largely imprints the cellular immune compartment and ...[more]

PMID: 24904583

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Project description:A major part of important mammalian respiratory allergens belongs to the lipocalin family of proteins. By this time, 19 respiratory mammalian lipocalin allergens have been registered in the WHO/IUIS Allergen Nomenclature Database. Originally, lipocalins, small extracellular proteins (molecular mass ca. 20 kDa), were characterized as transport proteins but they are currently known to exert a variety of biological functions. The three-dimensional structure of lipocalins is well-preserved, and lipocalin allergens can exhibit high amino acid identities, in several cases more than 50%. Lipocalins contain an internal ligand-binding site where they can harbor small principally hydrophobic molecules. Another characteristic feature is their capacity to bind to specific cell-surface receptors. In all, the physicochemical properties of lipocalin allergens do not offer any straightforward explanations for their allergenicity. Allergic sensitization begins at epithelial barriers where diverse insults through pattern recognition receptors awaken innate immunity. This front-line response is manifested by epithelial barrier-associated cytokines which together with other components of immunity can initiate the sensitization process. In the following, the crucial factor in allergic sensitization is interleukin (IL)-4 which is needed for stabilizing and promoting the type 2 immune response. The source for IL-4 has been searched widely. Candidates for it may be non-professional antigen-presenting cells, such as basophils or mast cells, as well as CD4+ T cells. The synthesis of IL-4 by CD4+ T cells requires T cell receptor engagement, i.e., the recognition of allergen peptides, which also provides the specificity for sensitization. Lipocalin and innate immunity-associated cell-surface receptors are implicated in facilitating the access of lipocalin allergens into the immune system. However, the significance of this for allergic sensitization is unclear, as the recognition by these receptors has been found to produce conflicting results. As to potential adjuvants associated with mammalian lipocalin allergens, the hydrophobic ligands transported by lipocalins have not been reported to enhance sensitization while it is justified to suppose that lipopolysaccharide plays a role in it. Taken together, type 2 immunity to lipocalin allergens appears to be a harmful immune response resulting from a combination of signals involving both the innate and adaptive immunities.

Project description:Allergens from furry animals frequently cause sensitization and respiratory allergic diseases. Most relevant mammalian respiratory allergens belong either to the protein family of lipocalins or secretoglobins. Their mechanism of sensitization remains largely unresolved. Mammalian lipocalin and secretoglobin allergens are associated with a function in chemical communication that involves abundant secretion into the environment, high stability and the ability to transport small volatile compounds. These properties are likely to contribute concomitantly to their allergenic potential. In this study, we aim to further elucidate the physiological function of lipocalin and secretoglobin allergens and link it to their sensitizing capacity, by analyzing their ligand-binding characteristics. We produced eight major mammalian respiratory allergens from four pet species in E.coli and compared their ligand-binding affinities to forty-nine ligands of different chemical classes by using a fluorescence-quenching assay. Furthermore, we solved the crystal-structure of the major guinea pig allergen Cav p 1, a typical lipocalin. Recombinant lipocalin and secretoglobin allergens are of high thermal stability with melting temperatures ranging from 65 to 90°C and strongly bind ligands with dissociation constants in the low micromolar range, particularly fatty acids, fatty alcohols and the terpene alcohol farnesol, that are associated with potential semiochemical and/or immune-modulating functions. Through the systematic screening of respiratory mammalian lipocalin and secretoglobin allergens with a large panel of potential ligands, we observed that total amino acid composition, as well as cavity shape and volume direct affinities to ligands of different chemical classes. Therefore, we were able to categorize lipocalin allergens over their ligand-binding profile into three sub-groups of a lipocalin clade that is associated with functions in chemical communication, thus strengthening the function of major mammalian respiratory allergens as semiochemical carriers. The promiscuous binding capability of hydrophobic ligands from environmental sources warrants further investigation regarding their impact on a molecule's allergenicity.

Dataset Information

Immune responses to inhalant Mammalian allergens.

Publications

Immune responses to inhalant Mammalian allergens.

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