L Gough1, H F Sewell, F Shakib. 1. Division of Molecular and Clinical Immunology, Faculty of Medicine and Health Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK.
Abstract
BACKGROUND: We have recently demonstrated that immunization of mice with proteolytically active Der p 1, the major dust mite allergen, results in a significant enhancement in total and Der p 1-specific IgE synthesis compared to mice immunized with Der p 1 that has been irreversibly blocked with the cysteine protease inhibitors E-64 and iodoacetamide. Thus, the demonstration that the proteolytic activity of Der p 1 enhances total IgE production, apart from increasing Der p 1-specific IgE, suggests that this allergen may have an IgE-specific adjuvant effect. OBJECTIVE: To determine if the proteolytic activity of Der p 1 has an IgE-specific adjuvant effect. METHODS: We have examined this concept in experiments whereby ovalbumin, used as a bystander antigen, was injected alone or coinjected with either proteolytically active or inactive Der p 1 into groups of mice and IgE and IgG antibody responses were measured. RESULTS: Here we demonstrate for the first time that the proteolytic activity of Der p 1, when given at 10-fold higher concentration, enhances the IgE antibody response to ovalbumin. CONCLUSIONS: These findings show that the proteolytic activity of Der p 1 leads to the augmentation of IgE antibody responses to itself and to other allergens present in the microenvironment.
BACKGROUND: We have recently demonstrated that immunization of mice with proteolytically active Der p 1, the major dust mite allergen, results in a significant enhancement in total and Der p 1-specific IgE synthesis compared to mice immunized with Der p 1 that has been irreversibly blocked with the cysteine protease inhibitors E-64 and iodoacetamide. Thus, the demonstration that the proteolytic activity of Der p 1 enhances total IgE production, apart from increasing Der p 1-specific IgE, suggests that this allergen may have an IgE-specific adjuvant effect. OBJECTIVE: To determine if the proteolytic activity of Der p 1 has an IgE-specific adjuvant effect. METHODS: We have examined this concept in experiments whereby ovalbumin, used as a bystander antigen, was injected alone or coinjected with either proteolytically active or inactive Der p 1 into groups of mice and IgE and IgG antibody responses were measured. RESULTS: Here we demonstrate for the first time that the proteolytic activity of Der p 1, when given at 10-fold higher concentration, enhances the IgE antibody response to ovalbumin. CONCLUSIONS: These findings show that the proteolytic activity of Der p 1 leads to the augmentation of IgE antibody responses to itself and to other allergens present in the microenvironment.
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