Cross-presentation of the long-lived lymphocytic choriomeningitis virus nucleoprotein does not require neosynthesis and is enhanced via heat shock proteins.
Many viral proteins that contain MHC class I-restricted peptides are long-lived, and it is elusive how they can give rise to class I epitopes. Recently, we showed that direct presentation of an epitope of the long-lived lymphocytic choriomeningitis virus nucleoprotein (LCMV-NP) required neosynthesis in accordance with the defective ribosomal products hypothesis. In this study, we report that LCMV-NP can be cross-primed in mice using either LCMV-NP-transfected human HEK293 or BALB/c-derived B8 cells as Ag donor cells. In addition, we establish that contrary to direct presentation, cross-presentation required accumulation of the mature LCMV-NP and could not be sustained by the newly synthesized LCMV-NP protein, intermediate proteasomal degradation products, or the minimal NP396 epitope. Nevertheless, NP cross-presentation was enhanced by heat shock and was blunted by inhibitors of heat shock protein 90 and gp96. We propose that cross-presentation has evolved to sustain the presentation of stable viral proteins when their neosynthesis has ceased in infected donor cells.
Department of Biology, Division of Immunology, University of Constance, Konstanz, Germany. bastas@post.queensu.ca
Sameh
S
Basta
Ricarda
R
Stoessel
Michael
M
Basler
Maries
M
van den Broek
Marcus
M
Groettrup
D000276:Adjuvants, Immunologic / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism / Q000502:physiology; D016923:Cell Death / Q000276:immunology / Q000528:radiation effects; D002460:Cell Line; D045142:Cross-Priming / Q000276:immunology*; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D018869:Heat-Shock Response / Q000276:immunology; D006801:Humans; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D056892:Mediator Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000276:immunology / Q000378:metabolism; D009698:Nucleoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000276:immunology / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000276:immunology; D012269:Ribosomal Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology; D015534:Trans-Activators / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D014466:Ultraviolet Rays
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; C113182:DRIP, VDR interacting protein complex; D018841:HSP90 Heat-Shock Proteins; D056892:Mediator Complex; D009687:Nuclear Proteins; D009698:Nucleoproteins; D010446:Peptide Fragments; D012269:Ribosomal Proteins; D015534:Trans-Activators; C094245:nucleoprotein peptide 394-408, lymphocytic choriomeningitis virus; C052646:sarcoma glycoprotein gp96 rejection antigens; D046988:Proteasome Endopeptidase Complex