Allergen Extracts Variable Fraction of Total Response to Are Differently Polarized and Account for a T Cell Responses to Known Allergen Proteins

A panel of 133 allergens derived from 28 different sources, including fungi, trees, grasses, weeds, and indoor allergens, was surveyed utilizing prediction of HLA class II-binding peptides and ELISPOT assays with PBMC from allergic donors, resulting in the identification of 257 T cell epitopes. More than 90% of the epitopes were novel, and for 14 allergen sources were the first ever identified to our knowledge. The epitopes identified in the different allergen sources summed up to a variable fraction of the total extract response. In cases of allergens in which the identified T cell epitopes accounted for a minor fraction of the extract response, fewer known protein sequences were available, suggesting that for low epitope coverage allergen sources, additional allergen proteins remain to be identified. IL-5 and IFN-g responses were measured as prototype Th2 and Th1 responses, respectively. Whereas in some cases (e.g., orchard grass, Alternaria, cypress, and Russian thistle) IL-5 production greatly exceeded IFN-g, in others (e.g., Aspergillus, Penicillum, and alder) the production of IFN-g exceeded IL-5. Thus, different allergen sources are associated with variable polarization of the responding T cells. The present study represents the most comprehensive survey to date of human allergen-derived T cell epitopes. These epitopes might be used to characterize T cell phenotype/T cell plasticity as a function of seasonality, or as a result of specific immunotherapy treatment or varying disease severity (asthma or rhinitis). A llergic reactions to common environmental allergens are associated with serious clinical manifestations, such as rhinitis and asthma, translating into high morbidity and societal costs. Furthermore, the incidence and prevalence of allergic disease are constantly rising. Current treatments for allergic disease are not fully satisfactory, and, coincidentally, our understanding of the fundamental aspects of allergic disease remains incomplete (1, 2). It is well appreciated that the initiation and maintenance of allergic disease are due to a complex series of molecular events, including both innate and adaptive immunity (3–5). In terms of adaptive immunity, IgE is of particular importance (6). Its cross-linking by Ag is a main cause of the release of histamine and other mediators and subsequent clinical manifestations of an allergic response (7). In fact, IgE reactivity is used to define the particular allergens contained in a given allergen source (8). However, in addition to IgE responses, T cells also vitally contribute to allergic disease (9). This contribution may be indirect, by promoting the production of IgE and the …