BACKGROUND: Effective immunotherapy for peanut allergy is hampered by a lack of understanding of peanut-reactive CD4(+) T cells. OBJECTIVE: To identify, characterize, and track Ara h 1-reactive cells in subjects with peanut allergy by using Ara h 1-specific class II tetramers. METHODS: Tetramer-guided epitope mapping was used to identify the antigenic peptides within the peanut allergen Ara h 1. Subsequently, HLA class II/Ara h 1-specific tetramers were used to determine the frequency and phenotype of Ara h 1-reactive T cells in subjects with peanut allergy. Cytokine profiles of Ara h 1-reactive T cells were also determined. RESULTS: Multiple Ara h 1 epitopes with defined HLA restriction were identified. Ara h 1-specific CD4(+) T cells were detected in all of the subjects with peanut allergy tested. Ara h 1-reactive T cells in subjects with allergy expressed CCR4 but did not express CRTH2. The percentage of Ara h1-reactive cells that expressed the β7 integrin was low compared with total CD4(+) T cells. Ara h 1- reactive cells that secreted IFN-γ, IL-4, IL-5, IL-10, and IL-17 were detected. CONCLUSION: In individuals with peanut allergy, Ara h 1-reactive T cells occurred at moderate frequencies, were predominantly CCR4(+) memory cells, and produced IL-4. Class II tetramers can be readily used to detect Ara h 1-reactive T cells in the peripheral blood of subjects with peanut allergy without in vitro expansion and would be effective for tracking peanut-reactive CD4(+) T cells during immunotherapy.
BACKGROUND: Effective immunotherapy for peanutallergy is hampered by a lack of understanding of peanut-reactive CD4(+) T cells. OBJECTIVE: To identify, characterize, and track Ara h 1-reactive cells in subjects with peanutallergy by using Ara h 1-specific class II tetramers. METHODS: Tetramer-guided epitope mapping was used to identify the antigenic peptides within the peanut allergen Ara h 1. Subsequently, HLA class II/Ara h 1-specific tetramers were used to determine the frequency and phenotype of Ara h 1-reactive T cells in subjects with peanutallergy. Cytokine profiles of Ara h 1-reactive T cells were also determined. RESULTS: Multiple Ara h 1 epitopes with defined HLA restriction were identified. Ara h 1-specific CD4(+) T cells were detected in all of the subjects with peanutallergy tested. Ara h 1-reactive T cells in subjects with allergy expressed CCR4 but did not express CRTH2. The percentage of Ara h1-reactive cells that expressed the β7 integrin was low compared with total CD4(+) T cells. Ara h 1- reactive cells that secreted IFN-γ, IL-4, IL-5, IL-10, and IL-17 were detected. CONCLUSION: In individuals with peanutallergy, Ara h 1-reactive T cells occurred at moderate frequencies, were predominantly CCR4(+) memory cells, and produced IL-4. Class II tetramers can be readily used to detect Ara h 1-reactive T cells in the peripheral blood of subjects with peanutallergy without in vitro expansion and would be effective for tracking peanut-reactive CD4(+) T cells during immunotherapy.
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