TY - JOUR
T1 - Major source of antigenic peptides for the MHC class I pathway is produced during the pioneer round of mRNA translation
AU - Apcher, Sebastien
AU - Daskalogianni, Chrysoula
AU - Lejeune, Fabrice
AU - Manoury, Beńed́icte
AU - Imhoos, Gabriela
AU - Heslop, Lea
AU - Fah̊raeus, Robin
PY - 2011/7/12
Y1 - 2011/7/12
N2 - 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.
AB - 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.
KW - MHC class I-restricted antigen presentation
KW - Pioneer round of translation
UR - http://www.scopus.com/inward/record.url?scp=79961016996&partnerID=8YFLogxK
U2 - 10.1073/pnas.1104104108
DO - 10.1073/pnas.1104104108
M3 - Article
C2 - 21709220
AN - SCOPUS:79961016996
SN - 0027-8424
VL - 108
SP - 11572
EP - 11577
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 28
ER -