Teaching/Research Area #2: Cellular Allergology

The area ‘Cellular Allergology’ includes cells of the innate and adaptive immune system with relevance for allergy, ex vivo systems to study cellular responses as well as in vivo systems based on experimental animal models.
The projects within this research area will we centered on basophils/mast cells, T and B lymphocytes and antigen-presenting cells. Along those lines basophil and mast cell function will be studied under the influence of targeted drugs impacting on kinase-inhibitors (project # 11), which have been introduced into human medicine during the last two decades. These projects will explore in how far the detrimental allergen-induced IgE-receptor signaling events can be abrogated or altered with the help of these drugs. Dissection of the involved signaling pathways and potential synergies between drugs will be evaluated.
Another important aspect of this research area is the detailed investigation of the allergen-specific T cell responses. The assembled Faculty members have greatly contributed to the characterization of allergen-specific T cell epitopes of major allergens, including Bet v 1, Art v 1, Amb a 1, Pru p 3, and Hev b 3. Moreover, the Speaker of this proposal and his coworkers have cloned and functionally characterized several human T cell receptors, which are specific for the major epitopes of the major birch pollen allergen Bet v 1 and the major mugwort pollen allergen, Art v 1. These tools are available for all Faculty members and facilitate the generation of high numbers of human allergen-specific T cells in a short period of time. To characterize the human allergen-specific T cell response further, CD4 T cells will be scrutinized in projects # 07, 09 and 15 for their signaling thresholds, their decisive actions leading to Th2 polarization and it will be asked how signal strength might impact on their development and how this might influence the fate of T cell phenotypes. The events leading to T cell-mediated pathology in atopic dermatitis will be studied by project # 02. Moreover, the human CD8+ T cell response to defined allergens will be studied herein (# 05) to clarify whether the effector or regulatory potential of such cells could be used to influence the overall T cellular immune response towards allergens for the mutual benefit of patients. Thirdly, innate immune responses of antigen-presenting cells (APC) will be addressed upon encounter with complex allergen formulations, such as whole pollen extracts. Studies dedicated to the detection of natural adjuvants within whole pollen and centered on the question how such adjuvants might interact and influence the innate immune response of antigen-presenting cells and how this in turn might impact on T cell polarization will be carried out by project # 14. Another strategy how to interfere with the ongoing activation of allergen-specific T cells would be the targeting of APC displaying allergen-specific peptides with soluble forms of high-affinity ligands for HLA-presented allergen fragments. For that purpose project # 07 plans to employ affinity-matured forms of allergen-specific T cell antigen receptors.  IgE-facilitated allergen presentation has been described as a potent mechanism for the activation of allergen-specific T cells. Project # 06 will use defined molecular probes to explore the underlying signaling events. Another aspect of research centered on APC will be dedicated to the exploration of the cytotoxic potential of APC (# 16) and by which means such cytotoxicity could be preferentially targeted to cells of interest.

Faculty Members – Research Groups: