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

CM Laumont, T Daouda, JP Laverdure… - Nature …, 2016 - nature.com
CM Laumont, T Daouda, JP Laverdure, É Bonneil, O Caron-Lizotte, MP Hardy, DP Granados…
Nature communications, 2016nature.com
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 …
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.
nature.com