CD8+ T cell cross-priming via transfer of proteasome substrates.
"Cross-priming" describes the activation of naïve CD8+ T cells by professional antigen-presenting cells that have acquired viral or tumor antigens from "donor" cells. Antigen transfer is believed to be mediated by donor cell-derived molecular chaperones bearing short peptide ligands generated by proteasome degradation of protein antigens. We show here that cross-priming is based on the transfer of proteasome substrates rather than peptides. These findings are potentially important for the rational design of vaccines that elicit CD8+ T cell responses.
Norbury
Christopher C
CC
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD, 20892-0440, USA.
Basta
Sameh
S
Donohue
Keri B
KB
Tscharke
David C
DC
Princiotta
Michael F
MF
Berglund
Peter
P
Gibbs
James
J
Bennink
Jack R
JR
Yewdell
Jonathan W
JW
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology* / Q000378:metabolism; D000956:Antigens, Viral / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D045142:Cross-Priming; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D007114:Immunization; D009980:Influenza A virus / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018832:Molecular Chaperones / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology; D046988:Proteasome Endopeptidase Complex; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D014612:Vaccines / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000502:physiology
D000941:Antigens; D000956:Antigens, Viral; D015853:Cysteine Proteinase Inhibitors; D018832:Molecular Chaperones; D009097:Multienzyme Complexes; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D014612:Vaccines; C067713:lactacystin; D010047:Ovalbumin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine