Diverse and highly cross‐reactive T‐cell responses in ragweed allergic patients independent of geographical region

Background Ragweed frequently causes seasonal allergies in North America and Europe. In the United States, several related ragweed species with diverse geographical distribution cause allergic symptoms. Cross‐reactivity towards related ragweed species of IgE and treatment‐induced IgG4 has been demonstrated previously. However, less is known about the underlying T‐cell cross‐reactivity. Methods The allergen content of ragweed extracts was determined by mass spectrometry and related to T‐cell epitopes of Amb a allergens (group 1, 3, 4, 5, 8 and 11) in 20 American ragweed allergic patients determined by FluoroSpot and proliferation assays. T‐cell responses to 50 frequently recognized Amb a‐derived T‐cell epitopes and homologous peptides from western ragweed (Amb p), giant ragweed (Amb t) and mugwort (Art v) were investigated in an additional 11 American and 14 Slovakian ragweed allergic donors. Results Ragweed extracts contained all known allergens and isoallergens thereof. Donor T‐cell responses were diverse and directed against all Amb a 1 isoallergens and to most minor allergens investigated. Similar response patterns were seen in American and Slovakia donors. Several epitopes were cross‐reactive between isoallergens and ragweed species, some even including mugwort. T‐cell cross‐reactivity generally correlated with allergen sequence homology. Conclusion T‐cell epitopes of multiple allergens/isoallergens are involved in the diverse T‐cell responses in ragweed allergic individuals. T‐cell lines were highly cross‐reactive to epitopes of related ragweed species without any apparent geographical response bias. These data support that different ragweed species can be considered an allergen homology group with Amb a as the representative species regarding diagnosis as well as allergy immunotherapy. T‐cell epitopes of multiple major and minor ragweed allergens/isoallergens are involved in the diverse T‐cell responses in ragweed allergic individuals. The T‐cells cross‐react to epitopes of related ragweed species and the same epitopes are important for American and European individuals. Extensive T‐cell and IgE cross‐reactivity support that related ragweed species can be considered an Amb a allergen homology group regarding diagnosis and immunotherapy treatment.