P03 Towards cure and prevention of birch pollen-related food allergy

Background: Birch pollen and birch pollen-related food allergy are highly prevalent in adult individuals and also affect children. Birch pollen-related food allergy results from sensitization to the major birch pollen allergen, Bet v 1, and subsequent cross-reaction of Bet v 1-specific IgE antibodies and T cells with structurally related proteins in certain foods, e.g. Mal d 1 in apple. In certain cases Bet v 1-related food allergy may even lead to life-threatening symptoms. Although Bet v 1 initiates this secondary food allergy, successful immunotherapy (AIT) of birch pollinosis often fails to improve food-induced symptoms. The immunological underpinnings that explain why cross-reactivity suffices to induce but not to cure birch pollen-related food allergy are still not entirely clear. 

Aim: To better characterize Bet v 1- and Mal d 1-specific cellular and humoral responses in a unique model of birch pollen-related food allergy in order to develop strategies to prevent and cure birch pollen-related food allergy.

Approach: In the first funding period of the Danube Allergy Research Cluster we successfully established the sorting and subsequent processing of allergen-specific T cells from allergic individuals for single cell sequencing. We now want to proceed with single cell transcriptomic profiling to obtain detailed insights into allergen-specific T cell responses in disease and following AIT. Allergen-specific T cells from samples collected in and out of the pollen season, after consumption of apple, as well as before and after sublingual immunotherapy (SLIT) with recombinant Bet v 1 (rBet v 1-SLIT) or Mal d 1 (rMal d 1-SLIT) will be profiled. The data from single cell sequencing will provide detailed insights into the dynamics, interrelationship, and clonal repertoires of the different subsets of Bet v 1-specific T cells. These results will be complemented by cellular assays that reveal the specificity, cross-reactivity, and epitope recognition of allergen-specific T cells. Moreover, we intend to better characterize the humoral processes underlying AIT-induced food tolerance by assessing the role of antibody affinity for protective function. We will separate SLIT-induced high and low affinity allergen-specific antibodies from individuals who did and did not develop tolerance to apples and compare their quantity and quality regarding IgE-blocking in basophil activation tests and facilitated antigen-presentation assays. 

Originality and Innovation: rMal d 1-SLIT improved apple allergy which could be associated with an altered T cell response and the induction of protective Mal d 1-specific antibodies. In contrast, rBet v 1-SLIT neither improved apple allergy nor induced antibodies protective against Mal d 1. Thus, the samples collected after either SLIT represent excellent tools to decipher the cellular and humoral mechanisms required for tolerance induction to birch pollen-related food. These results together with the deeper insights into the immune responses to natural allergen exposure will enhance our understanding of the disease-driving processes and contribute to the identification of possibilities for therapeutic and preventive intervention to reduce both, respiratory and food-induced symptoms. Beyond this, the findings gained from this project have great potential for the development of biomarkers to timely identify birch pollen-allergic patients at risk for developing food allergy.