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

LUZ MARÍA PALACIOS; FIAMA BOUCHARD; CINTIA ARAUJO FURLAN; NICOLAS DANIEL DHO; FEDERICO DANIEL RUIZ MORENO; BELKYS A. MALETTO; MARÍA INÉS CRESPO; GABRIEL MORÓN

San Luis

Congreso; LXXI Reunión 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 responseagainst antigens. In particular, DCs have the special ability to internalizeexogenous antigens and cross present (XP) them in MHCI context to inducecytotoxic CD8+ T cell (CTL) response, which can be potentially exploited forimmunotherapeutic purposes. Our group is interested in searching for newadjuvants able to improve CTL response. In that context, we performed a highthroughput screening (HTS) to identify new compounds that could potentiate XP,using an assay developed in our laboratory based on JAWSII DCs line and solubleOVA as antigen (sOVA). In this work, we analyzed the mechanisms underlyingXP potentiation of Pimozide (P), one of the 5 hits identified after HTS. Weobserved that P does not modify sOVA internalization, and neither MHC I-surfaceexpression in DCs. It has been reported that P accumulates in acidiccompartments and acts as a lysosomotropic drug. Thus, we studied if Paccumulates in lysosomes. After blocking endo phagosomal acidification, P effecton DCs XP was diminished. We also observed that incubation of DCs with Pincreased antigen translocation from endosomes to the cytosol, a key step in XP.Taking all these results into account, our evidence suggests that P affects endophagosomal processing of antigens on DCs. Further studies will be engaged tocompletely understand the mechanisms involved in enhancing XP.