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Nat Commun. 2016 Jan 5;7:10238. doi: 10.1038/ncomms10238.

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

Author information

1
Institute for Research in Immunology and Cancer, Université de Montréal, PO Box 6128 Station Centre-Ville, Montreal, Quebec, Canada H3C 3J7.
2
Department of Medicine, Faculty of Medicine, Université de Montréal, PO Box 6128 Station Centre-Ville, Montreal, Quebec, Canada H3C 3J7.
3
Department of Computer Science and Operations Research, Faculty of Arts and Sciences, Université de Montréal, PO Box 6128 Station Centre-Ville, Montreal, Quebec, Canada H3C 3J7.
4
Department of Chemistry, Université de Montréal, PO Box 6128 Station Centre-Ville, Montreal, Quebec, Canada H3C 3J7.
5
Division of Hematology, Hôpital Maisonneuve-Rosemont, 5415 de l'Assomption Boulevard, Montreal, Quebec, Canada H1T 2M4.

Abstract

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.

PMID:
26728094
PMCID:
PMC4728431
DOI:
10.1038/ncomms10238
[Indexed for MEDLINE]
Free PMC Article

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