Processing of some antigens by the standard proteasome but not by the immunoproteasome results in poor presentation by dendritic cells

By stimulating human lymphocytes with an autologous renal carcinoma, we obt ained CTL recognizing an antigen derived from a novel, ubiquitous protein. The CTL failed to lyse autologous EBV-transformed B cells, even though the latter express the protein. This is due to the presence in these cells of i mmunoproteasomes, which, unlike standard proteasomes, cannot produce the an tigenic peptide. We show that dendritic cells also carry immunoproteasomes and fail to present this antigen. This may explain why the relevant CTL esc ape thymic deletion and are not regularly activated in the periphery. Lack of cleavage by the immunoproteasome was also observed for melanoma differen tiation antigen Melan-A(26-35)/HLA-A2, currently used for antitumoral vacci nation. For immunization with such antigens, proteins should be less suitab le than peptides, which do not require proteasome digestion in dendritic ce lls.