Our proposal will use epitopes to comparatively evaluate immune responses in three different prototypic allergic diseases. We will study cockroach (CR) and mouse (MO) inhalation allergens, which are associated with the development of asthma in inner city children (Project 1); cow?s milk (CM), the most prevalently recognized pediatric food allergen (Project 2); and Aspergillus (ASP) and Alternaria (ALT) fungal allergens, which are associated with severe forms of asthma (Project 3). The extensive scientific overlap will offer opportunities for synergies between projects. Our study extensively utilizes cohorts independently funded by NIAID, to further multiply synergies and impact of the investigations. The evolution of responses will be examined as a function of time following natural exposure, exposure as part of work-duties and allergen immunotherapy (AIT). We will also study and compare individuals that are exposed but remain healthy, to people that have mild allergies and those that have severe asthma. Our hypothesis is that these distinct groups can be distinguished on the basis of their T cell response. Specifically, different groups might recognize different protein allergens or fragments (epitopes). It is also possible that the protein and genetic programs characteristic of T cells (T cell phenotypes) seen in allergic diseases of different types and severity will be unique. Our additional hypotheses are that evolution of T cell phenotypes can give us insights into the mechanism of allergic and asthmatic disease. If this were to be the case, it would have potential diagnostic value, and possibly suggest new therapeutic interventions.
T cell responses are a key component of allergic disease and definition of the actual epitope fragments derived from allergens and recognized from T cells allows accurate measurement, quantification and isolation of allergen-specific T cells. Our proposed research targets several important allergen systems: cockroach and mouse allergens because they correlate with asthma development in inner city, food allergens that are an important source of pediatric disease, and fungal allergens, whose recognition correlate with severe asthma. Definition of the exact features of these T cells will allow comparison of their molecular programs with the severity and evolution of clinical disease, and potentially suggest new diagnostic and therapeutic approaches.
|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|