Methods: To thoroughly map Bla g-derived T cell epitopes, cockroach extract was subjected to proteomic and transcriptomic analysis. PBMC from Bla g-sensitized subjects, with (n=55) or without (n=17) asthma, and non-Bla g-sensitized controls with Bla g-unrelated rhinitis (n=20) were analyzed. To characterize different TH functionalities of allergen-specific T cells, overlapping peptides from known allergens and novel antigens were assayed for their capacity to induce IL-5, IFNγ, IL-10, IL-17, and IL-21 production in PBMC.
Results: T cell responses in PBMC for 20 known and novel Bla g antigens (NBGA) were detected. This represents a >10-fold increase in cockroach-specific T cell targets compared to what has been reported in the literature to date. Cytokine responses of cockroach-sensitized individuals were predominantly TH2-polarized (IL-5), with higher response magnitude in patients with diagnosed asthma. Strikingly, the dominant antigens were different in asthmatic subjects (Bla g9 and 11) as compared to non-asthmatic sensitized (Bla g4, and the novel antigen NBGA5).
Conclusions: Asthmatic and non-asthmatic sensitized individuals exhibit similar functionality (predominantly TH2 polarized responses). Asthmatic individuals exhibit higher levels of cytokine producing T cells and different patterns of immunodominance. Moreover, many T cell epitopes identified here may present attractive targets for the development of a peptide-based cockroach-specific immunotherapy approach that circumvents IgE reactivity and any associated adverse reactions therefore rendering it suitable for asthmatics.