A lysosome protease inhibitor act as an adjuvant by increasing the half life of the co-administered Ag and by activating dendritic cells

CORIA, LORENA; IBAÑEZ, ANDRES; PASQUEVICH, KARINA ALEJANDRA; BRUNO, LAURA; CARABAJAL, MARIANELA; RISSO, GABRIELA; GONZÁLEZ COBIELLO, PAULA; FRANK, MARÍA FERNANDA; CASSATARO, JULIANA

Mar del Plata

Congreso; LIX Reunión Científica Anual de La Sociedad Argentina de Investigación Clínica, LXII Reunión Anual de la Sociedad Argentina de Inmunología; 2014

Sociedad Argentina de Inmunología y Sociedad Argentina de Investigación Clínica

Previous results demonstrated that a Brucella spp. protein (Bp) is a broad spectrum protease inhibitor as it can inhibit proteases present in the stomach and gut (mostly serine proteases) and also lysosomal proteases (cysteine proteases). Moreover, subcutaneous co-administration of Bp as adjuvant and ovalbumin (OVA) as model antigen (Ag) induces OVA specific IFN-γ producing CD8+ T cells and cytotoxic T cells in mice. In this work we characterized the mechanism of inhibition of Bp on cysteine proteases using a specific fluorogenic substrate for cathepsin L. We have found that Bp has a competitive mechanism of inhibition of cathepsin L with an inhibition constant in the µM range. We also found that Bp increases the amount of the co-administered Ag inside Lamp2+ compartments in dendritic cells (DCs) by confocal microscopy (P