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Clin Exp Allergy. 2016 Sep;46(9):1194-205. doi: 10.1111/cea.12772. Epub 2016 Jul 26.

Sequence conservation predicts T cell reactivity against ragweed allergens.

Author information

1
La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
2
Institute for Immunology and Infectious Diseases, Murdoch University, Perth, WA, Australia.
3
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.

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.

KEYWORDS:

T cell epitopes; allergens; ragweed

PMID:
27359111
PMCID:
PMC5007187
DOI:
10.1111/cea.12772
[Indexed for MEDLINE]
Free PMC Article

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