PIMOZIDE: A NOVEL/OLD DRUG THAT ENHANCES CROSS PRESENTATION OF ANTIGENS MEDIATING THE AUGMENT OF ANTIGEN TRANSLOCATION TO THE CYTOSOL IN DENDRITIC CELLS

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

San Luis

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

Sociedad Argentina de Inmunología

Dendritic cells (DCs) are professional Antigen Presenting Cells (APCs) responsible for activating naive T lymphocytes to induce specific response against antigens. In particular, DCs have the special ability to internalize exogenous antigens and cross present (XP) them in MHCI context to induce cytotoxic CD8+ T cell (CTL) response, which can be potentially exploited for immunotherapeutic purposes. Our group is interested in searching for new adjuvants able to improve CTL response. In that context, we performed a high throughput screening (HTS) to identify new compounds that could potentiate XP, using an assay developed in our laboratory based on JAWSII DCs line and soluble OVA as antigen (sOVA). In this work, we analyzed the mechanisms underlying XP potentiation of Pimozide (P), one of the 5 hits identified after HTS. We observed that P does not modify sOVA internalization, and neither MHC I-surface expression in DCs. It has been reported that P accumulates in acidic compartments and acts as a lysosomotropic drug. Thus westudied if P accumulates in lysosomes. After blocking endo phagosomal acidification, P effect on DCs XP was diminished. We also observed that incubation of DCs with P increased antigen translocation from endosomes to the cytosol, a key step in XP.Taking all these results into account, our evidence suggests that P affects endo phagosomal processing of antigens on DCs. Further studies will be engaged to completely understand the mechanisms involved in enhancing XP