Proteases as Th2 adjuvants

Abstract

Several cysteine and serine protease allergens have been cloned from house dust mites, including Der p 1, Der p 3, Der p 6, and Der p 9. A significant body of evidence suggests that these allergens mimic helper T (Th) 2 cell adjuvants. Der p 1 cleaves CD23 from activated B cells and CD25 from T cells. Der p 1 proteolytically degrades tight junctions in lung epithelium and causes release of proinflammatory cytokines from bronchial epithelial cells, mast cells, and basophils. These synergistic effects of mite enzyme allergens may promote IgE synthesis and have direct inflammatory effects on lung epithelium, which could explain why mite allergens are associated with asthma. The crystal structures of the proenzyme and mature forms of Der p 1 have been determined, as have the structures of other indoor allergens that are not enzymes (eg, Der p 2, Fel d 1, and Bla g 2). Cockroach allergens are strongly associated with asthma in US inner cities, yet none of the cockroach allergens that have been cloned are proteolytic enzymes. Thus although mite proteases allergens may act as Th2 adjuvants, a paradoxical effect is that other allergens may elicit strong Th2 responses in the absence of enzyme activity.