Our proposal focuses on cockroach (CR) and mouse (MO) allergens, dominant in inner city children correlated with development of allergic asthma later on in life. We also rely on epitopes from other allergens and tetanus toxoid (TT) and pertussis (PT) antigens, as important specificity controls. Our studies will answer the RFA question: ?Does the presence of T-cells with particular epitope specificities differentiate allergic from non-allergic individuals?? We have already detected significant differences, in both the CR and MO systems, supporting the rationale and feasibility of the proposed work. We will define epitopes with reactivity in non-allergics and allergics with different disease severities. We plan to next answer the questions; ?In persons with allergy, do specific T-cell epitopes differentiate between various clinical phenotypes or stages of disease severity? How important is the immunologic phenotype of epitope-specific T-cells as a marker of clinical presentation?? We will study samples taken over time from children from households at high-risk for asthma development. We will count the number of allergen-specific T cells, and define their pattern of protein expression and genetic profiles. Finally, we will ask: ?How stable is the epitope-specific T-cell repertoire over time and what are the clinical implications of natural alterations in the repertoire within individuals? Does allergen exposure or AIT influence a particular group of epitope-specific T-cells?? Samples from various donor cohorts will be characterized in terms of number of allergen-specific T cells, protein and genetic profiles. We will study samples from the CoNAC (Cockroach Nasal Allergen Challenge) study, performed by the ICAC network, in sensitized and non-sensitized donors. We will also examine longitudinal samples from an in-house established cohort of donors that are MO non-sensitized but, because of occupational duties, heavily exposed to MO allergens. Finally, we will study longitudinal samples from immunotherapy clinical trials including individuals treated with CR extract or placebo. We will measure the evolution of responses to CR allergens. In addition, we will measure responses to other allergens to which donors are either sensitized or non-sensitized to establish whether immunotherapy only modulates CR responses, or also modulates T cells specific for other allergens.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1)
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La Jolla Institute for Immunology
La Jolla
United States
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Schulten, Véronique; Westernberg, Luise; Birrueta, Giovanni et al. (2018) Allergen and Epitope Targets of Mouse-Specific T Cell Responses in Allergy and Asthma. Front Immunol 9:235
Glesner, Jill; Filep, Stephanie; Vailes, Lisa D et al. (2018) Allergen content in German cockroach extracts and sensitization profiles to a new expanded set of cockroach allergens determine in vitro extract potency for IgE reactivity. J Allergy Clin Immunol :
da Silva Antunes, Ricardo; Pham, John; McMurtrey, Curtis et al. (2018) Urinary Peptides As a Novel Source of T Cell Allergen Epitopes. Front Immunol 9:886
Birrueta, Giovanni; Tripple, Victoria; Pham, John et al. (2018) Peanut-specific T cell responses in patients with different clinical reactivity. PLoS One 13:e0204620