The allergic T cell response against mouse proteins

Abstract

Abstract Mouse allergy is rising in prevalence, affecting inner-city households and laboratory workers. Increased exposure to mice in inner-city households is a strong predictor for asthmatic disease. Despite a strong link between mouse exposure and asthmatic disease, the allergic immune response to mouse has been significantly understudied. To date, only one major allergen in mouse, Mus m 1, has been identified and very little is known about the targets of the allergic immune response against mouse. Using a proteomic/transcriptomic approach, we sought to identify T cell targets in 24 mouse allergic and asthmatic patients. Mouse urine and epithelial extracts were analyzed by 2D-IgE/IgG immunoblots using pooled sera from mouse-sensitized donors. Mass spectrometry of selected protein spots identified 30 novel antibody reactive proteins. Predicted MHC binding peptides from these novel proteins and mouse homologs to mammalian allergens were screened for T cell reactivity in PBMCs from mouse allergic patients. Overlapping peptides from the major mouse allergen Mus m 1 and its major urinary protein isoforms were screened in parallel. T cell epitope mapping experiments showed that responses to Mus m 1 peptides were dominant overall. However, reactivity to mouse peptides homologous to other mammalian allergens, specifically guinea pig, was also detected. In summary, our data demonstrates that the cellular and serological targets of the allergic response overlap, with Mus m 1 being the major target for both T cells and IgE antibodies. However, on a serological level, other proteins are also recognized. To the best of our knowledge, this is one of the first comprehensive studies of T cell epitope targets in mouse allergy.