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Exploiting non-canonical translation to identify new targets for T cell-based cancer immunotherapy | Cellular and Molecular Life Sciences
Description:
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.
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pubmed, article, google, scholar, cas, central, cell, translation, human, class, mhc, van, nat, reading, peptides, cancer, antigen, immunol, nature, biol, med, cells, exp, open, res, mol, cryptic, initiation, rev, gene, perreault, frames, ribosomal, protein, sci, acids, peptide, nucleic, lymphocytes, alternative, codon, complex, usa, response, atkins, readthrough, frameshifting, molecules, proc, natl,
Topics {✒️}
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- Van Deutekom HW, Kesmir C (2015) Zooming into the binding groove of HLA molecules: which positions and which substitutions change peptide binding most?
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headline:Exploiting non-canonical translation to identify new targets for T cell-based cancer immunotherapy
description: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.
datePublished:2017-08-19T00:00:00Z
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Major histocompatibility complex class I
Cytotoxic T cells
Antigen processing
Antigen presentation
Protein synthesis
Neoantigens
Cell Biology
Biomedicine
general
Life Sciences
Biochemistry
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headline:Exploiting non-canonical translation to identify new targets for T cell-based cancer immunotherapy
description: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.
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Major histocompatibility complex class I
Cytotoxic T cells
Antigen processing
Antigen presentation
Protein synthesis
Neoantigens
Cell Biology
Biomedicine
general
Life Sciences
Biochemistry
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