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Global proteogenomic analysis of human MHC class I-associated peptides derived from non-canonical reading frames.

Céline M LaumontTariq DaoudaJean-Philippe LaverdureÉric BonneilOlivier Caron-LizotteMarie-Pierre HardyDiana P GranadosChantal DuretteSébastien LemieuxPierre ThibaultClaude Perreault
Published in: Nature communications (2016)
In view of recent reports documenting pervasive translation outside of canonical protein-coding sequences, we wished to determine the proportion of major histocompatibility complex (MHC) class I-associated peptides (MAPs) derived from non-canonical reading frames. Here we perform proteogenomic analyses of MAPs eluted from human B cells using high-throughput mass spectrometry to probe the six-frame translation of the B-cell transcriptome. We report that ∼ 10% of MAPs originate from allegedly noncoding genomic sequences or exonic out-of-frame translation. The biogenesis and properties of these 'cryptic MAPs' differ from those of conventional MAPs. Cryptic MAPs come from very short proteins with atypical C termini, and are coded by transcripts bearing long 3'UTRs enriched in destabilizing elements. Relative to conventional MAPs, cryptic MAPs display different MHC class I-binding preferences and harbour more genomic polymorphisms, some of which are immunogenic. Cryptic MAPs increase the complexity of the MAP repertoire and enhance the scope of CD8 T-cell immunosurveillance.
Keyphrases
  • high throughput
  • mass spectrometry
  • endothelial cells
  • gene expression
  • working memory
  • dna methylation
  • genome wide
  • emergency department
  • amino acid
  • copy number
  • single cell
  • quantum dots
  • rna seq
  • small molecule
  • dna binding