A major house dust mite allergen disrupts the immunoglobulin E network by selectively cleaving CD23: innate protection by antiproteases.

Hewitt, Colin R. A.; Brown, Alan R.; Hart, Barbara; Pritchard, David

doi:10.1084/jem.182.5.1537

Cited by 268 publications

(198 citation statements)

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“…29) and the IL-2R␣ chain (30), and by modifying the balance between IFN-␥ and IL-4 (66,67). Furthermore, the proteolytic activity of Der P I enhances titers of IgE specific for the protease (68) and bystander Ags such as OVA (69).…”

Section: Discussionmentioning

confidence: 99%

A Protease-Activated Pathway Underlying Th Cell Type 2 Activation and Allergic Lung Disease

Kheradmand

Kiss

et al. 2002

The Journal of Immunology

288

292

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The respiratory allergens that induce experimental Th cell type 2-dependent allergic lung inflammation may be grouped into two functional classes. One class of allergens, in this study termed type I, requires priming with adjuvants remote from the lung to overcome airway tolerogenic mechanisms that ordinarily preclude allergic responses to inhaled Ags. In contrast, the other, or type II, allergen class requires neither remote priming nor additional adjuvants to overcome airway tolerance and elicit robust allergic lung disease. In this study, we show in an experimental model that diverse type II allergens share in common proteolytic activity that is both necessary and sufficient for overcoming airway tolerance and induction of pulmonary allergic disease. Inactivated protease and protease-free Ag fragments showed no allergenic potency, demonstrating that only active protease acting on endogenous substrates was essential. Furthermore, induction of airway tolerance could be aborted and allergic lung disease established by simply adding purified protease to a type I allergen. Thus, exogenous proteases are common to type II allergens and may be generally required to overcome the innate resistance of the airway to Th cell type 2 activation and allergic inflammation, raising concern for their potential contribution to diseases such as asthma.

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Section: Discussionmentioning

confidence: 99%

A Protease-Activated Pathway Underlying Th Cell Type 2 Activation and Allergic Lung Disease

Kheradmand

Kiss

et al. 2002

The Journal of Immunology

288

292

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“…Cysteine protease activity of our preparations of rDer p 1 and rDer f 1 also crucially commits to the sensitization process in mice (37). Although Phillips et al (60) reported that Der p 1 stimulated purified human basophils to release IL-4, whether its cysteine protease activity is responsible for the basophil activation is unknown because their Der p 1 preparation also contained serine proteases other than Der p 1 (28,61). Whether the rDer f 1 and rDer p 1, which show cysteine protease activity but no serine protease activity (15), could stimulate basophils to produce Th2-inducing cytokines should be addressed in a future study.…”

Section: Discussionmentioning

confidence: 99%

Modulation of Allergenicity of Major House Dust Mite Allergens Der f 1 and Der p 1 by Interaction with an Endogenous Ligand

Takai¹,

Kato²,

Hatanaka

et al. 2009

The Journal of Immunology

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Although many allergens bind endogenous molecules other than Abs in the human body, whether the interaction can modulate allergenicity has been unknown. Here, we investigated the effect of the interaction of recombinant major mite group 1 allergens (Der f 1 and Der p 1), which belong to the papain-like cysteine protease family, with an endogenous protease inhibitor, cystatin A, on their allergenicity. Cystatin A bound reduced forms of the allergens, in which the cysteine residue at the catalytic center of the protease activity was reduced by treatment with l-cysteine, but did not bind oxidized forms. Cystatin A partially inhibited the binding of IgE in mite-allergic volunteers’ sera to the reduced forms, but unexpectedly enhanced the basophil histamine-releasing activity. A catalytic site-mutant of Der f 1 behaved in terms of histamine release, similarly to the reduced form. Molecular modeling showed that cystatin A interacts with the allergens within a narrow area. The results indicate that interaction with cystatin A reduces the limited number of IgE epitopes of the allergens but enhances their biological activity to release histamine, suggesting a new concept, that interaction between allergens and their endogenous ligands modulates the allergenicity even toward enhancement in the effector phase. On the other hand, i.p. immunization without alum of mice with cystatin A-treated reduced Der f 1 induced less serum Der f 1-specific IgE than immunization with reduced Der f 1 alone, suggesting that endogenous protease inhibitors suppress the induction of allergen-specific IgE, which is dependent on the enzymatic activity of cysteine protease-allergens, in the sensitization process.

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“…15 de cisteína-proteasa como la papaína de la papaya (Carica papaya) y la bromelaína extraida de la piña (Ananas comosus) se les han demostrado propiedades alergénicas [2-51. Al Der p 1 también se le ha sugerido alguna función digestiva debido a su localización en la región gastrointestinal del ácaro y su concentración alta (0,l-0,2 nglpartícula) en la partícula fecal del ácaro (6, 7).…”

Section: %unclassified

“…Además, por su actividad enzimática, Der p 1 separa al CD23 de la membrana de los linfocitos B, alterando así la regulación de la producción de IgE (15). Los anteriores hallazgos parecen apoyar la idea de que la actividad de cisteína-proteasa de Der p 1 influya también en la patogénesis del asma alérgica.…”

Section: Cm#randabkanr Porcinounclassified

Alergenos: relación entre función biológica y alergenicidad

1998

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ResumenLos alergenos se encuentran en muy diversas fuentes, pero, tienen la particularidad de inducir la producción de inmunoglobulina E (IgE) y provocar alergia. No se conoce una característica molecular biológica común entre los alergenos que explique su capacidad alergénica. En los últimos años, se han demostrado o inferido diferentes funciones biológicas en los alergenos, generando nuevas hipótesis sobre el papel de dichas funciones en la actividad alergénica. Con el fin de identificar qué funciones biológicas se han demostrado o inferido en los alergenos y analizar su posible influencia en el papel alergénico, se revisaron aproximadamente doscientos alergenos teniendo como base los ya caracterizados por el Comité de Nomenclatura de Alergenos de la OMS, como también otros menos caracterizados pero con algunas propiedades fisico~~liímicas conocidas. Los alergenos se agruparon de acuerdo con la actividad biológica y se tabularon con su fuente de origen, peso molecular (PM), punto isoeléctrico (pl), frecuencia de reactividad en la población alérgica, potenciales sitios de glicosilación y formación de enlaces disulfuro. Se identificaron 88 alergenos en los que se ha informado alguna actividad biológica. El agrupamiento de estos según la actividad produjo los siguientes resultados: enzimática (47,2%), inhibición de enzimas (11,3%), transporte (18,1%), regulación de la actividad celular (15,9%) y otras actividades como la de conferir resistencia a enfermedades en plantas y citólisis (7,9%). En muchos de estos alergenos, la actividad biológica ha sido inferida por su homología estructural con proteínas de función conocida, pero los experimentos que corroboren dicha función no se han realizado. La mayoría de estos alergenos tienen en común PM<60 kDa, p1<7,0 y escasa formación de oligómeros. Nuestro análisis sugiere que la capacidad de inducir alergia no está determinada por ninguna de las funciones biológicas descritas. Aunque la actividad de cisterna-proteasa y serina-proteasa de algunos de los alergenos de los ácaros domésticos han sido señaladas como determinantes en el papel alergénico en dichos alergenos, los datos experimentales no son concluyentes y no permiten atribuir la alergenicidad a la función enzimática. Allergens: the relationship between biological function and allergenicityAllergens can be found from many diverse sources but they have the particular quality of being able to induce immunoglobulin E (IgE) production and to provoke allergy. A common biological molecular characteristic which can explain their allergenic capacity is not known amongst the allergens. In the last few years allergens' different biological functions have been demonstrated or inferred, generating a new hypothesis about the role of the said functions in allergenic activity. To identify which biological functions have Instituto de Investigaciones Inmunológicas, Universidad de Cartagena Recibido para su publicación: enero 15 de 1998.

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A major house dust mite allergen disrupts the immunoglobulin E network by selectively cleaving CD23: innate protection by antiproteases.

Cited by 268 publications

References 50 publications

A Protease-Activated Pathway Underlying Th Cell Type 2 Activation and Allergic Lung Disease

A Protease-Activated Pathway Underlying Th Cell Type 2 Activation and Allergic Lung Disease

Modulation of Allergenicity of Major House Dust Mite Allergens Der f 1 and Der p 1 by Interaction with an Endogenous Ligand

Alergenos: relación entre función biológica y alergenicidad

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