13 Intriguingly, we found that treatment of BL cells MK-2206 cost with proteasome inhibitors partially restores their capacity to present the EBNA1 epitope, thereby suggesting that proteasomes from BL cells, although less active against prototype substrate peptides, which only partially indicate the in vivo proteasomal activities, degrade the HPV epitope during the processing of EBNA1. It

remains to be elucidated whether other EBNA1-derived CTL epitopes may be more efficiently generated and presented after partial inhibition of proteasomes or whether this effect is restricted to the HPV epitope. In conclusion, our study, together with previous reports, strongly supports the idea Selleck Small molecule library that EBNA1-specific CTLs might be exploited therapeutically to target EBV-positive malignancies in combination with chemotherapy and protocols designed to restore antigen-presenting capacity in the tumour. In this context, it has been recently demonstrated that tubacin, a molecule that inhibits histone deacetylase 6, demonstrates a fairly selective capacity

to induce apoptosis in BL cells, but not in LCLs.37 Furthermore, the combination of tubacin with a proteasome inhibitor induced efficient killing of BL cells,37 which are known to be resistant to proteasome inhibitor-induced apoptosis.21,38 These findings, together with those reported in this study, suggest that the use of proteasome inhibitors, alone or in combination with other drugs such as tubacin, may represent a strategy Isotretinoin for the treatment of EBNA1-carrying

tumours, because proteasome inhibitors, in addition to their effect as pro-apoptotic drugs, may also increase the immunogenicity of EBNA1, thereby resulting in the efficient elimination of EBNA1-positive malignancies. This work was supported by grants from the University of Ferrara and Fondazione Cassa di Risparmio di Ferrara. We are grateful to A. Forster for editorial assistance and to Dr A. Balboni for HLA typing. The authors have no financial conflicts of interest. Table S1. MHC class I expression in lymphoblastoid cell line and in Burkitt’s lymphoma cells. “
“EAE, an animal model for multiple sclerosis, is a Th17- and Th1-cell-mediated auto-immune disease, but the mechanisms leading to priming of encephalitogenicTcells in autoimmune neuroinflammation are poorly understood. To investigate the role of dendritic cells (DCs) in the initiation of autoimmuneTh17- andTh1-cell responses andEAE, we used mice transgenic for a simian diphtheria toxin receptor (DTR) expressed under the control of the murineCD11c promoter (CD11c-DTRmice onC57BL/6 background).EAEwas induced by immunization with myelin oligodendrocyte glycoprotein (MOG) protein in CFA.