Open AccessMajor source of antigenic peptides for the MHC class I pathway is produced during the pioneer round of mRNA translation
Author(s) -
Sébastien Apcher,
Chrysoula Daskalogianni,
Fabrice Lejeune,
Bénédicte Manoury,
Gabriela Imhoos,
Lea Heslop,
Robin Fåhræus
Publication year - 2011
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1104104108
Subject(s) - translation (biology) , biology , eif4e , messenger rna , protein biosynthesis , major histocompatibility complex , antigen processing , nonsense mediated decay , mhc class i , antigen , microbiology and biotechnology , antigen presentation , immune system , eukaryotic translation , genetics , rna , t cell , gene , rna splicing
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.