Distinct characteristics of seasonal (Bet v 1) vs. perennial (Der p 1/Der p 2) allergen-specific CD4⁺ T cell responses

Summary: Background A better understanding of allergen-specific CD4⁺ T cell responses is needed to help improving immunological therapies.Objective To compare CD4⁺ T cell responses against seasonal (Bet v 1) and perennial (Der p 1, Der p 2) allergens.Methods Major histocompatibility complex class II peptide tetramers were engineered to monitor allergen-specific T cell responses. After in vitro expansion, tetramer⁺ cells were tested for surface markers using cytofluorometry. Cytokine gene expression and production were assessed using quantitative PCR and cytokine surface capture assays, respectively.Results Tetramer⁺ cells were detected in 19 patients allergic to house dust mites (HDM), seven allergic to birch pollen, 13 allergic to both and nine non-allergics with either an HLA-DRB1^*0101, ^*0301, ^*1501 or an HLA-DPB1^*0401 background. High-avidity T cells are elicited against the immunodominant Bet v 1_141-155 epitope, whereas broader low-avidity T cell responses are induced against Der p 1_16-30,_110-124,_171-185 and Der p 2_{26-40,107-121} epitopes. Responses against Bet v 1 involve effector (CDL62 low, CCR7 low) or central (CD62L⁺, CCR7⁺) memory cells in allergic and non-allergic individuals, respectively, whereas central memory cells are mostly detected against mite allergens. In non-allergics, both mite and Bet v 1-specific T cells produce IFN-γ and IL-10. In contrast to Bet v 1-driven Th2 responses, mite allergens induce highly polymorphic responses in allergics, including Th1, Th2/Th17 or mixed Th1/Th2 profiles. Mite-specific T cell frequencies in the blood remain in the range of 1-6 × 10^-4 CD4⁺ T cells throughout the year.Conclusion Different memory CD4⁺ T cell responses are elicited in the context of chronic vs. seasonal stimulation with the allergen(s). The heterogeneity in the patterns of CD4⁺ T cell responses observed in patients allergic to HDMs should be taken into account for specific immunotherapy.