Cross-Presentation of Listeria-Derived CD8 T Cell Epitopes Requires Unstable Bacterial Translation Products

Abstract

Presentation of bacteria-derived CD8 T cell epitopes by dendritic cells (DC) requires either their direct infection or that DC acquire and cross-present Ags from other infected cells. We found that cross-presentation of Listeria monocytogenes-derived CD8 T cell epitopes was much stronger than direct Ag presentation by infected murine DC. Cross-presentation of Listeria-derived CD8 T cell epitopes showed unique physiological requirements. It was dependent upon the delivery of unstable bacterial translation products by infected, but still viable, Ag donor cells. Cross-presentation was enhanced both when unstable translation products in infected Ag donor cells were protected from proteasomal degradation and when the production of misfolded bacterial proteins was increased. The requirement of unstable translation products for cross-presentation may represent a novel pathway that functions to focus the CD8 T cell response toward epitopes derived from newly synthesized proteins.

A deterministic model for the processing and presentation of bacteria-derived antigenic peptides

“…Thus from model III it can be predicted that after Ag uptake by external loading or by cross-presentation antigenic peptides will be presented most efficiently if they are rapidly degraded and yield stable peptide/MHC complexes. Interestingly, this prediction is in line with the observation that the cross-presentation of L. monocytogenes-derived antigenic peptides requires the uptake by DC of a instable but not finally processed Ag from infected cells (Janda et al, 2004). As can be inferred from Eq.…”

Cross-Presentation of the Long-Lived Lymphocytic Choriomeningitis Virus Nucleoprotein Does Not Require Neosynthesis and Is Enhanced via Heat Shock Proteins

“…Besides, a role for HSP in cross-presentation was either not addressed or indirectly looked at (20 -23, 49), while others have reported that LCMV-NP does not access the cross-priming pathway (19). Of a particular interest is the data reported by Janda et al (49) examining secreted bacterial proteins with a half-life of 90 min in ADCs (49) and reporting, in contrast to our findings, that unstable bacterial translation products were more efficient than mature proteins as an antigenic source for cross-presentation. In this system, the proteins examined for crosspresentation were synthesized in the bacterium before being secreted in the cytosol of infected cells.…”

Placental Leucine Aminopeptidase Efficiently Generates Mature Antigenic Peptides In Vitro but in Patterns Distinct from Endoplasmic Reticulum Aminopeptidase 1

“…To evaluate the ability of PLAP to generate 9mer model antigenic peptides from 10mer precursors we analyzed the trimming of 7 model 10mer peptides, 5 of which correspond to naturally occurring antigenic peptide precursors. Three of the peptides we tested (sequences IRLRPGGKKK, KSLYNTVATL and KGYKDGNEYI) correspond to natural precursors of epitopes found to be cross-presented (34, 35). Figure 3 demonstrates characteristic chromatograms from trimming reactions highlighting accumulated products.…”