Human memory CD4+ T cell response to the major dog allergen Can f 5, prostatic kallikrein

Summary Background Human CD 4+ T cell responses to important animal allergens are still insufficiently understood. Objective To comprehensively characterize in vitro and ex vivo the peripheral blood memory CD 4+ T cell responses of subjects with and without allergy to the major dog allergen Can f 5, the only known animal allergen in the kallikrein family of proteins. Methods Can f 5‐specific memory CD 4+ T cell lines ( TCL s) were established from the peripheral blood of 12 subjects with and 12 subjects without allergy to Can f 5 and characterized for their functional and phenotypic properties. The results were evaluated with those obtained ex vivo with a novel CD 154 enrichment method. The epitopes recognized by the Can f 5‐specific TCL s were determined with 72 overlapping 16‐mer peptides covering the sequence of the allergen. Results Can f 5‐specific TCL s were obtained at about tenfold higher frequency from allergic than from non‐allergic subjects. Functionally, the TCL s of allergic subjects displayed a Th2‐biased cytokine phenotype and increased T cell receptor avidity, whereas the TCL s of non‐allergic subjects displayed a Th1‐/Th0‐biased cytokine phenotype and lower TCR avidity. The higher frequency and the Th2 phenotype of Can f 5‐specific memory CD 4+ T cells in allergic subjects were confirmed by the CD 154 enrichment method ex vivo . Six distinct T cell epitope regions of Can f 5 were predominantly recognized by the TCL s from allergic subjects. Conclusions and Clinical Relevance Can f 5‐specific memory CD 4+ T cell responses differ considerably between subjects with and without allergy, as assessed by both in vitro and ex vivo approaches. Peptides containing the dominant T cell epitopes of Can f 5 can be employed for developing peptide‐based immunotherapy for dog allergy.