Abstract
Mouse allergy has become increasingly common, mainly affecting laboratory workers and inner-city households. To date, only one major allergen, namely Mus m 1, has been described. We sought to identify T cell targets in mouse allergic patients. PBMC from allergic donors were expanded with either murine urine or epithelial extract and subsequently screened for cytokine production (IL-5 and IFNγ) in response to overlapping peptides spanning the entire Mus m 1 sequence, peptides from various Mus m 1 isoforms [major urinary proteins (MUPs)], peptides from mouse orthologs of known allergens from other mammalian species and peptides from proteins identified by immunoproteomic analysis of IgE/IgG immunoblots of mouse urine and epithelial extracts. This approach let to the identification of 106 non-redundant T cell epitopes derived from 35 antigens. Three major T cell-activating regions were defined in Mus m 1 alone. Moreover, our data show that immunodominant epitopes were largely shared between Mus m 1 and other MUPs even from different species, suggesting that sequence conservation in different allergens is a determinant for immunodominance. We further identified several novel mouse T cell antigens based on their homology to known mammalian allergens. Analysis of cohort-specific T cell responses revealed that rhinitis and asthmatic patients recognized different epitope repertoires. Epitopes defined herein can be formulated into an epitope “megapool” used to diagnose mouse allergy and study mouse-specific T cell responses directly ex vivo. This analysis of T cell epitopes provides a good basis for future studies to increase our understanding of the immunopathology associated with MO-allergy and asthma.
Highlights
Mouse (MO) allergies are of growing importance in children and adults alike as they are potent sensitizers [1] and MO allergies are prevalent in the United States, especially in inner city populations [2, 3]
To define Mus m 1 T cell epitopes recognized in MO allergic individuals, PBMC from allergic donors were expanded with either urine or epithelial extracts, and cytokine responses (IL-5 and IFNγ) were determined following 24 h restimulation using overlapping peptides spanning the entire Mus m 1 sequence
To the best of our knowledge, this is the first study focused on mouse-specific T cell responses in mouse-sensitized asthmatic and rhinitic patients
Summary
Mouse (MO) allergies are of growing importance in children and adults alike as they are potent sensitizers [1] and MO allergies are prevalent in the United States, especially in inner city populations [2, 3]. A study of children in American inner cities reported that 18% have positive mouse skin test responses [1]. Prevalence of mouse sensitization of 10–26% have been reported [4, 5] in cohorts of animal-care workers, exposed to MO allergens because of occupational duties. MO-specific IgE is associated with early wheeze and atopy in inner-city birth cohorts. The odds ratio for onset of wheezing by age 3 is 4.6 for MO-sensitized children and remarkably rises to 9.7 in children cosensitized to MO and cockroach [6], another pestrelated allergy commonly found in inner cities. High IgE titers to MO and to German cockroach (CR) have been associated with atopic dermatitis [6]
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