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Cellular and Molecular Life Sciences

, Volume 75, Issue 4, pp 607–621 | Cite as

Exploiting non-canonical translation to identify new targets for T cell-based cancer immunotherapy

  • Céline M. Laumont
  • Claude PerreaultEmail author
Review

Abstract

Cryptic MHC I-associated peptides (MAPs) are produced via two mechanisms: translation of protein-coding genes in non-canonical reading frames and translation of allegedly non-coding sequences. In general, cryptic MAPs are coded by relatively short open reading frames whose translation can be regulated at the level of initiation, elongation or termination. In contrast to conventional MAPs, the processing of cryptic MAPs is frequently proteasome independent. The existence of cryptic MAPs derived from allegedly non-coding regions enlarges the scope of CD8 T cell immunosurveillance from a mere ~2% to as much as ~75% of the human genome. Considering that 99% of cancer-specific mutations are located in those allegedly non-coding regions, cryptic MAPs could furthermore represent a particularly rich source of tumor-specific antigens. However, extensive proteogenomic analyses will be required to determine the breath as well as the temporal and spatial plasticity of the cryptic MAP repertoire in normal and neoplastic cells.

Keywords

Major histocompatibility complex class I Cytotoxic T cells Antigen processing Antigen presentation Protein synthesis Neoantigens 

Abbreviations

AS

Ankylosing spondylitis

B-LCL

B-lymphoblastoid cell line

DRiP

Defective ribosomal product

eIF

Eukaryotic initiation factor

ER

Endoplasmic reticulum

HLA

Human leukocyte antigen

MAP

MHC I-associated peptide

Met-tRNAiMet

Methionine-loaded initiator tRNA

MHC I

Major histocompatibility complex class I

MS

Mass spectrometry

mTEC

Medullary thymic epithelial cell

ORF

Open reading frame

PRF

Programmed ribosomal frameshifting

TAP

Transporter associated with antigen processing

TSA

Tumor-specific antigen

Notes

Acknowledgements

Research performed in the authors’ lab was supported by a Grant from the Quebec Breast Cancer Foundation. C. M. L. is supported by a Cole Foundation fellowship. C. P. holds the Canadian Research Chair in Immunobiology. We apologize to authors whose work has not been cited due to space limitations.

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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Institute for Research in Immunology and CancerUniversité de MontréalMontrealCanada
  2. 2.Department of Medicine, Faculty of MedicineUniversité de MontréalMontrealCanada
  3. 3.Division of HematologyHôpital Maisonneuve-RosemontMontrealCanada

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