Format

Send to

Choose Destination
Cell Mol Life Sci. 2018 Feb;75(4):607-621. doi: 10.1007/s00018-017-2628-4. Epub 2017 Aug 19.

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

Author information

1
Institute for Research in Immunology and Cancer, Université de Montréal, Station Centre-Ville, PO Box 6128, Montreal, QC, H3C 3J7, Canada.
2
Department of Medicine, Faculty of Medicine, Université de Montréal, Station Centre-Ville, PO Box 6128, Montreal, QC, H3C 3J7, Canada.
3
Institute for Research in Immunology and Cancer, Université de Montréal, Station Centre-Ville, PO Box 6128, Montreal, QC, H3C 3J7, Canada. claude.perreault@umontreal.ca.
4
Department of Medicine, Faculty of Medicine, Université de Montréal, Station Centre-Ville, PO Box 6128, Montreal, QC, H3C 3J7, Canada. claude.perreault@umontreal.ca.
5
Division of Hematology, Hôpital Maisonneuve-Rosemont, 5415 de l'Assomption Boulevard, Montreal, QC, H1T 2M4, Canada. claude.perreault@umontreal.ca.

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:

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

PMID:
28823056
DOI:
10.1007/s00018-017-2628-4
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center