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.
Basta
Sameh
S
Department of Biology, Division of Immunology, University of Constance, Konstanz, Germany. bastas@post.queensu.ca
Stoessel
Ricarda
R
Basler
Michael
M
van den Broek
Maries
M
Groettrup
Marcus
M
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