Journal article
Sequence conservation predicts T cell reactivity against ragweed allergens
Clinical & Experimental Allergy, Vol.46(9), pp.1194-1205
2016
Abstract
Background
Ragweed is a major cause of seasonal allergy, affecting millions of people worldwide. Several allergens have been defined based on IgE reactivity, but their relative immunogenicity in terms of T cell responses has not been studied.
Objective
We comprehensively characterized T cell responses from atopic, ragweed-allergic subjects to Amb a 1, Amb a 3, Amb a 4, Amb a 5, Amb a 6, Amb a 8, Amb a 9, Amb a 10, Amb a 11, and Amb p 5 and examined their correlation with serological reactivity and sequence conservation in other allergens.
Methods
Peripheral blood mononuclear cells (PBMCs) from donors positive for IgE towards ragweed extracts after in vitro expansion for secretion of IL-5 (a representative Th2 cytokine) and IFN-γ (Th1) in response to a panel of overlapping peptides spanning the above-listed allergens were assessed.
Results
Three previously identified dominant T cell epitopes (Amb a 1 176–191, 200–215, and 344–359) were confirmed, and three novel dominant epitopes (Amb a 1 280–295, 304–319, and 320–335) were identified. Amb a 1, the dominant IgE allergen, was also the dominant T cell allergen, but dominance patterns for T cell and IgE responses for the other ragweed allergens did not correlate. Dominance for T cell responses correlated with conservation of ragweed epitopes with sequences of other well-known allergens.
Conclusions and Clinical Relevance
These results provide the first assessment of the hierarchy of T cell reactivity in ragweed allergens, which is distinct from that observed for IgE reactivity and influenced by T cell epitope sequence conservation. The results suggest that ragweed allergens associated with lesser IgE reactivity and significant T cell reactivity may be targeted for T cell immunotherapy, and further support the development of immunotherapies against epitopes conserved across species to generate broad reactivity against many common allergens.
Details
- Title
- Sequence conservation predicts T cell reactivity against ragweed allergens
- Authors/Creators
- J. Pham (Author/Creator)C. Oseroff (Author/Creator)D. Hinz (Author/Creator)J. Sidney (Author/Creator)S. Paul (Author/Creator)J. Greenbaum (Author/Creator)R. Vita (Author/Creator)E. Phillips (Author/Creator)S. Mallal (Author/Creator)B. Peters (Author/Creator)A. Sette (Author/Creator)
- Publication Details
- Clinical & Experimental Allergy, Vol.46(9), pp.1194-1205
- Publisher
- Blackwell Publishing
- Identifiers
- 991005543343907891
- Copyright
- © 2016 John Wiley & Sons, Inc.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.65 Allergy
- 1.65.264 Allergy Mechanisms
- Web Of Science research areas
- Allergy
- Immunology
- ESI research areas
- Immunology