UNVEILING THE ROLE OF LIPID METABOLISM IN ENHANCING ANTIGEN CROSSPRESENTATION BY PERHEXILINE MALEATE-STIMULATED DENDRITIC CELLS

BOUCHARD, FIAMA; PALACIOS, LUZ MARÍA; DHO, NICOLÁS DANIEL; ARAUJO FURLÁN, CINTIA; RUIZ MORENO, FEDERICO; MALETTO, BELKYS ANGÉLICA; MORÓN, GABRIEL; CRESPO, MARÍA INÉS

San Luis

Congreso; LXXI REUNION ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2023

Sociedad Argentina de Inmunología

The immune response mediated by cytotoxic CD8+ T cells (CTLs) plays a pivotal role in bothtumor immunotherapy and defense against intracellular pathogens. Dendritic cells (DCs)have the ability to internalize and present exogenous antigens (Ag) via MHC I to activatenaïve CD8+ T cells, a process termed cross-presentation. Adjuvants are necessary to robustCTL response, especially in subunit vaccines. However, due to the intricate nature of Agcross-presentation pathways, identifying therapeutic targets that can serve as adjuvants forgenerating protective CTL responses has proven challenging. To address this, wepreviously performed a high throughput screening of drug libraries approved by internationalagencies. The aim was to identify novel compounds and molecular pathways capable ofenhancing Ag cross-presentation in DCs. Our approach involved the adaptation of the B3Zpresentation assay using the JAWSII DC cell line and Ovalbumin (OVA) as the soluble Ag.In this study, we elucidate the mechanisms underlying the enhancement of crosspresentation by Perhexiline Maleate (PM), one of the five active compounds identified.Notably, PM does not influence OVA internalization nor MHC I-surface expression in JAWSIIDCs. Moreover, incubating JAWSII DCs with PM led to increased translocation of Ags fromendosomes to the cytosol (p