Modulation of allergenicity of major house dust mite allergens Der f 1 and Der p 1 by interaction with an endogenous ligand

The Journal of Immunology : Official Journal of the American Association of Immunologists
Toshiro TakaiKo Okumura

Abstract

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 m...Continue Reading

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Citations

Aug 21, 2013·PloS One·Yoshimasa ImotoShigeharu Fujieda
Jan 13, 2016·Journal of Proteome Research·Jintarat ChoopongAnchalee Tungtrongchitr
Apr 5, 2011·Allergy, Asthma & Immunology Research·Keisuke ObokiHirohisa Saito
Mar 26, 2014·Allergology International : Official Journal of the Japanese Society of Allergology·Hideo IidaShigaku Ikeda
Mar 24, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Seiji KamijoToshiro Takai
Apr 3, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Seiji KamijoToshiro Takai
Dec 22, 2010·Allergology International : Official Journal of the Japanese Society of Allergology·Toshiro Takai, Shigaku Ikeda
Aug 5, 2010·Biochimica Et Biophysica Acta·Andy ChevignéMoreno Galleni

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