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Defective ribosomal products are the major source of antigenic peptides endogenously generated from influenza A virus neuraminidase.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2010 Feb 01; Vol. 184 (3), pp. 1419-24. Date of Electronic Publication: 2009 Dec 28. - Publication Year :
- 2010
-
Abstract
- The defective ribosomal product (DRiP) hypothesis of endogenous Ag processing posits that rapidly degraded forms of nascent proteins are a major source of peptide ligands for MHC class I molecules. Although there is broad experimental support for the DRiP hypothesis, careful kinetic analysis of the generation of defined peptide class I complexes has been limited to studies of recombinant vaccinia viruses expressing genes derived from other organisms. In this study, we show that insertion of the SIINFEKL peptide into the stalk of influenza A virus neuraminidase (NA) does not detectably modify NA folding, degradation, transport, or sp. act. when expressed in its natural context of influenza A virus infection. Using the 25-D1.16 mAb specific for K(b)-SIINFEKL to precisely quantitate cell surface complexes by flow cytometry, we demonstrate that SIINFEKL is generated in complete lockstep with initiation and abrogation of NA biosynthesis in both L-K(b) fibroblast cells and DC2.4 dendritic/monocyte cells. SIINFEKL presentation requires active proteasomes and TAP, consistent with its generation from a cytosolic DRiP pool. From the difference in the shutoff kinetics of K(b)-SIINFEKL complex expression following protein synthesis versus proteasome inhibition, we estimate that the t(1/2) of the biosynthetic source of NA peptide is approximately 5 min. These observations extend the relevance of the DRiP hypothesis to viral proteins generated in their natural context.
- Subjects :
- Amino Acid Sequence
Animals
Antigens, Viral metabolism
Cell Line
Dendritic Cells enzymology
Dendritic Cells immunology
Dendritic Cells virology
Dogs
Enzyme Activation immunology
Enzyme Stability immunology
Epitopes biosynthesis
Epitopes metabolism
Fibroblasts enzymology
Fibroblasts immunology
Fibroblasts virology
H-2 Antigens biosynthesis
H-2 Antigens metabolism
L Cells
Mice
Molecular Sequence Data
Monocytes enzymology
Monocytes immunology
Monocytes virology
Neuraminidase biosynthesis
Orthomyxoviridae Infections enzymology
Orthomyxoviridae Infections immunology
Orthomyxoviridae Infections virology
Ovalbumin metabolism
Ovalbumin physiology
Peptide Fragments metabolism
Peptide Fragments physiology
Protein Folding
Protein Transport immunology
Ribosomal Proteins metabolism
Antigen Presentation immunology
Antigens, Viral biosynthesis
Influenza A Virus, H1N1 Subtype enzymology
Influenza A Virus, H1N1 Subtype immunology
Neuraminidase metabolism
Protein Biosynthesis immunology
Ribosomal Proteins biosynthesis
Ribosomal Proteins deficiency
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 184
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 20038640
- Full Text :
- https://doi.org/10.4049/jimmunol.0901907