Role of tripeptidyl peptidase II in the processing of Listeria monocytogenes-derived MHC class I-presented antigenic peptides

The effective control of the infection of mice with the facultatively intracellular bacterium Listeria monocytogenes requires CD8 T cells which recognize bacterial antigenic peptides presented in the context of host MHC class I molecules. It is generally accepted that bacterial antigens are processed by the proteasome, a proteolytic cytoplasmic multiprotein complex. We observed that presentation of the L. monocytogenes-derived CD8 T cell epitope LLO 91–99 by infected cells can not be totally suppressed by inhibitors of the proteasome alone. Further analysis revealed that inhibitors of the cytoplasmic tripeptidyl peptidase II suppressed the presentation of the epitopes LLO 91–99 and p60 449–457. While significant suppression of the presentation of LLO 91–99 required the simultaneous inhibition of the proteasome and tripeptidyl peptidase II, presentation of p60 449–457 was suppressed by inhibitors of either the proteasome or TPPII alone. Thus, these data indicate that both, the proteasome and tripeptidyl protease II play a role in the processing of L. monocytogenes-derived antigenic peptides.