Ribosomal Proteins Regulate MHC Class I Peptide Generation for Immunosurveillance.
Fiche publication
Date publication
janvier 2019
Journal
Molecular cell
Auteurs
Membres identifiés du Cancéropôle Est :
Dr MARCHAND Virginie
Tous les auteurs :
Wei J, Kishton RJ, Angel M, Conn CS, Dalla-Venezia N, Marcel V, Vincent A, Catez F, Ferré S, Ayadi L, Marchand V, Dersh D, Gibbs JS, Ivanov IP, Fridlyand N, Couté Y, Diaz JJ, Qian SB, Staudt LM, Restifo NP, Yewdell JW
Lien Pubmed
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.
Mots clés
MHC-I antigen presentation, immunosurveillance, ribosomal protein
Référence
Mol. Cell. 2019 Jan 24;: