Highly heterogeneous Phl p 5-specific T cells from patients with allergic rhinitis differentially recognize recombinant Phl p 5 isoallergens

Abstract

Background: The prevalence of atopic allergy to Poaceae grasses poses a serious health problem.

Objective: To evaluate the T cell-activating capacity of recombinant grass pollen allergens suggested for immunotherapy, we characterized the T-cell response of allergic patients to the Phleum pratense (Phl p) major allergen, Phl p 5.

Methods: Thirty-eight Phl p 5-specific CD4(+) T-cell clones (TCCs) were isolated from the peripheral blood of 3 patients with allergic rhinitis and were characterized with respect to cross-reactivity, HLA restriction, cytokine profiles, and isoallergen specificity when tested with natural Phl p 5 and 5 rPhl p 5 isoallergens (4 Phl p 5a and 1 Phl p 5b).

Results: The TCCs were highly cross-reactive with group 5 allergens of related grasses, and the different cross-reactivity patterns found indicate that several T-cell epitopes are present in Phl p 5. Most TCCs displayed a TH0-like cytokine profile, whereas a few TCCs belonged to the TH2 or TH1 subset. The TCCs were restricted by HLA-DR (24/38 TCCs), HLA-DQ (11/38 TCCs), or HLA-DP (3/38 TCCs). Interestingly, 4 of the 34 TCCs tested reacted exclusively with the 4 rPhl p 5a isoforms; 8 of 34 TCCs were rPhl p 5b specific, and 3 of 34 TCCs reacted with all isoforms; 19 of 34 TCCs did not react with any of the rPhl p 5 isoallergens. Moreover, the overall isoform recognition pattern differed considerably among patients.

Conclusion: These results demonstrate that Phl p 5-specific T cells are highly heterogeneous and that individual TCCs, and individual patients, differentially recognize isoallergens. The differential isoallergen recognition for Phl p 5-specific T cells suggests, if confirmed in larger patient groups, that a combination of 2 or more rPhl p 5 isoallergens may be needed to replace the natural grass allergen for immunotherapy.