title: Global proteogenomic analysis of human MHC class I-associated peptides derived from non-canonical reading frames.
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.
authors.affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, PO Box 6128 Station Centre-Ville, Montreal, Quebec, Canada H3C 3J7.|Department of Medicine, Faculty of Medicine, Université de Montréal, PO Box 6128 Station Centre-Ville, Montreal, Quebec, Canada H3C 3J7.
authors.forename: Céline M
authors.initials: CM
authors.lastname: Laumont
authors.affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, PO Box 6128 Station Centre-Ville, Montreal, Quebec, Canada H3C 3J7.|Department of Medicine, Faculty of Medicine, Université de Montréal, PO Box 6128 Station Centre-Ville, Montreal, Quebec, Canada H3C 3J7.|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.
authors.forename: Tariq
authors.initials: T
authors.lastname: Daouda
authors.affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, PO Box 6128 Station Centre-Ville, Montreal, Quebec, Canada H3C 3J7.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Laverdure
authors.affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, PO Box 6128 Station Centre-Ville, Montreal, Quebec, Canada H3C 3J7.
authors.forename: Éric
authors.initials: É
authors.lastname: Bonneil
authors.affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, PO Box 6128 Station Centre-Ville, Montreal, Quebec, Canada H3C 3J7.
authors.forename: Olivier
authors.initials: O
authors.lastname: Caron-Lizotte
authors.affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, PO Box 6128 Station Centre-Ville, Montreal, Quebec, Canada H3C 3J7.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Hardy
authors.affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, PO Box 6128 Station Centre-Ville, Montreal, Quebec, Canada H3C 3J7.|Department of Medicine, Faculty of Medicine, Université de Montréal, PO Box 6128 Station Centre-Ville, Montreal, Quebec, Canada H3C 3J7.
authors.forename: Diana P
authors.initials: DP
authors.lastname: Granados
authors.affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, PO Box 6128 Station Centre-Ville, Montreal, Quebec, Canada H3C 3J7.
authors.forename: Chantal
authors.initials: C
authors.lastname: Durette
authors.affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, PO Box 6128 Station Centre-Ville, Montreal, Quebec, Canada H3C 3J7.|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.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lemieux
authors.affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, PO Box 6128 Station Centre-Ville, Montreal, Quebec, Canada H3C 3J7.|Department of Chemistry, Université de Montréal, PO Box 6128 Station Centre-Ville, Montreal, Quebec, Canada H3C 3J7.
authors.forename: Pierre
authors.initials: P
authors.lastname: Thibault
authors.affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, PO Box 6128 Station Centre-Ville, Montreal, Quebec, Canada H3C 3J7.|Department of Medicine, Faculty of Medicine, Université de Montréal, PO Box 6128 Station Centre-Ville, Montreal, Quebec, Canada H3C 3J7.|Division of Hematology, Hôpital Maisonneuve-Rosemont, 5415 de l'Assomption Boulevard, Montreal, Quebec, Canada H1T 2M4.
authors.forename: Claude
authors.identifier: http://orcid.org/0000-0001-9453-7383
authors.initials: C
authors.lastname: Perreault
mesh_terms: D005786:Gene Expression Regulation; D005805:Genes, MHC Class I / Q000235:genetics*; D005838:Genotype; D006801:Humans; D016133:Polymerase Chain Reaction; D040901:Proteomics / Q000379:methods*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016364:Reading Frames
chemical_list: D012333:RNA, Messenger