Ribosomal Proteins Regulate MHC Class I Peptide Generation for Immunosurveillance.
Animals
Antigen Presentation
Cell Line, Tumor
Coculture Techniques
HEK293 Cells
Histocompatibility Antigens Class I
/ biosynthesis
Host-Pathogen Interactions
Humans
Immunologic Surveillance
Influenza A virus
/ immunology
Melanoma
/ immunology
Mice, Inbred C57BL
Mice, Transgenic
Ribosomal Proteins
/ genetics
Ribosome Subunits, Large, Eukaryotic
/ genetics
Ribosome Subunits, Small, Eukaryotic
/ genetics
Skin Neoplasms
/ immunology
T-Lymphocytes
/ immunology
MHC-I antigen presentation
immunosurveillance
ribosomal protein
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
21 03 2019
21 03 2019
Historique:
received:
13
07
2018
revised:
29
10
2018
accepted:
21
12
2018
pubmed:
5
2
2019
medline:
15
9
2020
entrez:
5
2
2019
Statut:
ppublish
Résumé
The MHC class I antigen presentation system enables T cell immunosurveillance of cancers and viruses. A substantial fraction of the immunopeptidome derives from rapidly degraded nascent polypeptides (DRiPs). By knocking down each of the 80 ribosomal proteins, we identified proteins that modulate peptide generation without altering source protein expression. We show that 60S ribosomal proteins L6 (RPL6) and RPL28, which are adjacent on the ribosome, play opposite roles in generating an influenza A virus-encoded peptide. Depleting RPL6 decreases ubiquitin-dependent peptide presentation, whereas depleting RPL28 increases ubiquitin-dependent and -independent peptide presentation. 40S ribosomal protein S28 (RPS28) knockdown increases total peptide supply in uninfected cells by increasing DRiP synthesis from non-canonical translation of "untranslated" regions and non-AUG start codons and sensitizes tumor cells for T cell targeting. Our findings raise the possibility of modulating immunosurveillance by pharmaceutical targeting ribosomes.
Identifiants
pubmed: 30712990
pii: S1097-2765(18)31096-7
doi: 10.1016/j.molcel.2018.12.020
pmc: PMC6697054
mid: NIHMS1519606
pii:
doi:
Substances chimiques
Histocompatibility Antigens Class I
0
RPL28 protein, human
0
RPS28 protein, human
0
Ribosomal Proteins
0
ribosomal protein L6
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1162-1173.e5Subventions
Organisme : NIA NIH HHS
ID : R01 AG042400
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 AI000542-20
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 AI000542-21
Pays : United States
Informations de copyright
Published by Elsevier Inc.
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