Quantitating protein synthesis, degradation, and endogenous antigen processing.
Using L929 cells, we quantitated the macroeconomics of protein synthesis and degradation and the microeconomics of producing MHC class I associated peptides from viral translation products. To maintain a content of 2.6 x 10(9) proteins, each cell's 6 x 10(6) ribosomes produce 4 x 10(6) proteins min(-1). Each of the cell's 8 x 10(5) proteasomes degrades 2.5 substrates min(-1), creating one MHC class I-peptide complex for each 500-3000 viral translation products degraded. The efficiency of complex formation is similar in dendritic cells and macrophages, which play a critical role in activating T cells in vivo. Proteasomes create antigenic peptides at different efficiencies from two distinct substrate pools: rapidly degraded newly synthesized proteins that clearly represent defective ribosomal products (DRiPs) and a less rapidly degraded pool in which DRiPs may also predominate.
Princiotta
Michael F
MF
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
Finzi
Diana
D
Qian
Shu-Bing
SB
Gibbs
James
J
Schuchmann
Sebastian
S
Buttgereit
Frank
F
Bennink
Jack R
JR
Yewdell
Jonathan W
JW
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004734:Energy Metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D008024:Ligands; D051379:Mice; D018448:Models, Immunological; D009097:Multienzyme Complexes / Q000378:metabolism; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism
D015395:Histocompatibility Antigens Class I; D008024:Ligands; D009097:Multienzyme Complexes; D010455:Peptides; D011506:Proteins; D011993:Recombinant Fusion Proteins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex