Abstract
Worldwide, more than 1 billion people suffer from allergic diseases. However, until now it is not fully understood how certain proteins can induce allergic immune responses, while others cannot. Studies suggest that allergenicity is a process not only determined by properties of the allergen itself but also by costimulatory factors, that are not classically associated with allergic reactions. To investigate the allergenicity of the major birch pollen allergen Bet v 1 and the impact of adjuvants associated with pollen, e.g. lipopolysaccharide (LPS), we performed quantitative proteome analysis to study the activation of monocyte-derived dendritic cells (moDCs). Thus, we treated cells with birch pollen extract (BPE), recombinant Bet v 1, and LPS followed by proteomic profiling via high-performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS) using isobaric labelling. Enrichment and pathway analysis revealed the influence of regulated proteins especially in cytokine signalling and dendritic cell activation. We found highly regulated, but differentially expressed proteins after treatment with BPE and LPS, whereas the cellular response to Bet v 1 was limited. Our findings lead to the conclusion that Bet v 1 needs a specific “allergen context” involving cofactors apart from LPS to induce an immune response in human moDCs.
Highlights
How certain proteins can cause allergic sensitization in some individuals while not in others is still an open question, even if the process of allergic sensitization is quite well understood on a cellular level
Because LPS is frequently present in birch pollen extracts as ubiquitous contaminant, which show a higher efficacy in SIT compared to the recombinant allergen, we aimed at studying the differences in the effects of a recombinant variant of Bet v 1.0101, birch pollen extract (BPE), and pure LPS on human monocyte-derived dendritic cells (moDCs)
We used high-performance liquid chromatography (HPLC)-MS-based proteome analysis to compare the effects of the major birch pollen allergen Bet v 1 and BPE in order to elucidate the allergenicity of Bet v 1
Summary
How certain proteins can cause allergic sensitization in some individuals while not in others is still an open question, even if the process of allergic sensitization is quite well understood on a cellular level. An important factor seems to be the individual allergenicity of a protein, which describes the property of an antigen to cause an allergic immune response[18]. Pivotal pollen-derived cofactors can for instance be pollen associated lipid mediators, capable of inhibiting IL-12 production in DCs and inducing a TH2 preferring milieu[23] It was reported, that pollen extracts contain substantial amounts of serine proteases[24] or NAD(P)H oxidases[25], both showing immunostimulatory effects. To generate hypotheses regarding the underlying mechanisms in allergic immune responses and to identify determinants of allergenicity, a wholistic view on the complex interaction network of proteins in immunity is required. Shotgun proteomics is a suitable tool for more systemic investigations, overcoming the limitations of the techniques described above and providing a more comprehensive picture of the complexity of allergic immune responses[30]
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