Analysis of T cell responses to the major allergens from German cockroach: Epitope specificity and relationship to IgE production

Carla Oseroff, John Sidney, Victoria Tripple, Howard Grey, Robert A Wood, David H. Broide, Jason Greenbaum, Ravi Kolla, Bjoern Peters, X. Anna Pomés, Alessandro Sette

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Abstract

Bla g allergens are major targets of IgE responses associated with cockroach allergies. However, little is known about corresponding T cell responses, despite their potential involvement in immunopathology and the clinical efficacy of specific immunotherapy. Bioinformatic predictions of the capacity of Bla g 1, 2, 4, 5, 6, and 7 peptides to bind HLA-DR, -DP, and -DQ molecules, and PBMC responses from 30 allergic donors, identified 25 T cell epitopes. Five immunodominant epitopes accounted for more than half of the response. Bla g 5, the most dominant allergen, accounted for 65% of the response, and Bla g 6 accounted for 20%. Bla g 5 induced both IL-5 and IFN-γ responses, whereas Bla g 6 induced mostly IL-5, and, conversely, Bla g 2 induced only IFN-γ. Thus, responses to allergens within a source are independently regulated, suggesting a critical role for the allergen itself, and not extraneous stimulation from other allergens or copresented immunomodulators. In comparing Ab with T cell responses for several donor/allergen combinations, we detected IgE titers in the absence of detectable T cell responses, suggesting that unlinked T cell-B cell help might support development of IgE responses. Finally, specific immunotherapy resulted in IL-5 downmodulation, which was not associated with development of IFN-γ or IL-10 responses to any of the Bla g-derived peptides. In summary, the characteristics of T cell responses to Bla g allergens appear uncorrelated with IgE responses. Monitoring these responses may therefore yield important information relevant to understanding cockroach allergies and their treatment. Copyright

Original languageEnglish (US)
Pages (from-to)679-688
Number of pages10
JournalJournal of Immunology
Volume189
Issue number2
DOIs
StatePublished - Jul 15 2012

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ASJC Scopus subject areas

  • Immunology

Cite this

Oseroff, C., Sidney, J., Tripple, V., Grey, H., Wood, R. A., Broide, D. H., Greenbaum, J., Kolla, R., Peters, B., Anna Pomés, X., & Sette, A. (2012). Analysis of T cell responses to the major allergens from German cockroach: Epitope specificity and relationship to IgE production. Journal of Immunology, 189(2), 679-688. https://doi.org/10.4049/jimmunol.1200694