Major source of antigenic peptides for the MHC class I pathway is produced during the pioneer round of mRNA translation

Sebastien Apcher, Chrysoula Daskalogianni, Fabrice Lejeune, Beńed́icte Manoury, Gabriela Imhoos, Lea Heslop, Robin Fah̊raeus

Résultats de recherche: Contribution à un journalArticleRevue par des pairs

127 Citations (Scopus)

Résumé

The MHC class I antigen presentation pathway allows the immune system to distinguish between self and nonself. Despite extensive research on the processing of antigenic peptides, little is known about their origin. Here, we show that mRNAs carrying premature stop codons that prevent the production of full-length proteins via the nonsense-mediated decay pathway still produce a majority of peptide substrates for the MHC class I pathway by a noncanonical mRNA translation process. Blocking the interaction of the translation initiation factor eIF4E with the cap structure suppresses the synthesis of full-length proteins but has only a limited effect on the production of antigenic peptides. These results reveal an essential cell biological function for a class of translation products derived during the pioneer round of mRNA translation and will have important implications for understanding how the immune system detects cells harboring pathogens and generates tolerance.

langue originaleAnglais
Pages (de - à)11572-11577
Nombre de pages6
journalProceedings of the National Academy of Sciences of the United States of America
Volume108
Numéro de publication28
Les DOIs
étatPublié - 12 juil. 2011
Modification externeOui

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