title: Immune response to n-terminal and c-terminal deletion mutants of Aspergillus fumigatus major allergen ASP F 3.
abstract: The ubiquitous fungus Aspergillus fumigatus causes allergic rhinitis, asthma, sinusitis and allergic bronchopulmonary aspergillosis. A number of major allergens from A. fumigatus are purified, but their structure-function role in the pathogenesis of disease is not known. Such information is essential for devising alternative therapy of fungal allergic diseases. In the present study, N-terminal and C-terminal deletion mutants ofAsp f 3 were constructed and their immunopathological responses studied in a mice model of allergy. Three mutants viz,Asp f 3 (aa 33-168), (aa 1-142), and (aa 23-142) were made by deleting certain amino acids from epitopic regions of full lengthAsp f 3, a major allergen of A. furnigatus. TheAsp f 3 and three mutated proteins were expressed in pET vector. The C-terminal deletion mutantAsp f 3 (aa 1-142) induced elevated IFN-γ but low levels of IL-4 by spleen cells. This mutant also showed significant downregulation of peripheral blood eosinophils and lung inflammation in immunized mice. The N-terminal deletion mutantAsp f 3 (aa 33-168) also exhibited an immuno-suppressive effect in terms of IgE production and induction of Th2 cytokine. The results indicate thatrAsp f 3 and its deletion mutants induced distinct immune-inflammatory responses in mice on challenge with these proteins. The non-IgE binding deletion mutants ofAsp f 3 (aa 1-142 and aa 33-168) could deviate Th2 immune response with a concomitant reduction in airway inflammation and infiltration of inflammatory cells.
authors.affiliation: Allergy and Immunology Section, Institute of Genomics and Integrative Biology, Delhi University Campus, Mall Road, 110007 Delhi, India.
authors.forename: Bhanu P
authors.initials: BP
authors.lastname: Singh
authors.forename: Banani
authors.initials: B
authors.lastname: Banerjee
authors.forename: Puspanita
authors.initials: P
authors.lastname: Naik
authors.forename: Jordan N
authors.initials: JN
authors.lastname: Fink
authors.forename: Viswanath P
authors.initials: VP
authors.lastname: Kurup
keywords: ABPA; Aspergillus fumigatus; Deletion mutants; Murine model; rAsp f 3