Cross-presentation of Listeria-derived CD8 T cell epitopes requires unstable bacterial translation products.
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.
Janda
Jozef
J
Institut für Medizinische Mikrobiologie und Hygiene, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Mannheim, Germany.
Schöneberger
Petra
P
Skoberne
Mojca
M
Messerle
Martin
M
Rüssmann
Holger
H
Geginat
Gernot
G
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D001427:Bacterial Toxins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D002460:Cell Line; D004269:DNA, Bacterial / Q000096:biosynthesis / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006460:Hemolysin Proteins; D008089:Listeria monocytogenes / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis / Q000276:immunology; D011499:Protein Processing, Post-Translational / Q000276:immunology
C078516:60 kDa protein, Listeria monocytogenes; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004269:DNA, Bacterial; D018984:Epitopes, T-Lymphocyte; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D010446:Peptide Fragments; C038705:hlyA protein, Listeria monocytogenes