MORÓN VÍCTOR GABRIEL
Congresos y reuniones científicas
Título:
PIMOZIDE: A NOVEL/OLD DRUG THAT ENHANCES CROSS PRESENTATION OF ANTIGENS MEDIATING THE AUGMENT OF ANTIGEN TRANSLOCATION TO THE CYTOSOL IN DENDRITIC CELLS
Lugar:
San Luis
Reunión:
Congreso; LXXI Reunión de la Sociedad Argentina de Inmunología; 2023
Institución organizadora:
Sociedad Argentina de Inmunología
Resumen:
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, we studied 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.
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, we studied 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.
