Premium
Sequence conservation predicts T cell reactivity against ragweed allergens
Author(s) -
Pham J.,
Oseroff C.,
Hinz D.,
Sidney J.,
Paul S.,
Greenbaum J.,
Vita R.,
Phillips E.,
Mallal S.,
Peters B.,
Sette A.
Publication year - 2016
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12772
Subject(s) - ragweed , immunology , allergen , epitope , immunoglobulin e , biology , peripheral blood mononuclear cell , allergy , immunogenicity , virology , antibody , in vitro , genetics
Summary 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 ( PBMC s) 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.