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

Abstract:

: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.

authors

Apcher S,Daskalogianni C,Lejeune F,Manoury B,Imhoos G,Heslop L,Fåhraeus R

doi

10.1073/pnas.1104104108

subject

Has Abstract

pub_date

2011-07-12 00:00:00

pages

11572-7

issue

28

eissn

0027-8424

issn

1091-6490

pii

1104104108

journal_volume

108

pub_type

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