title: MHC I-associated peptides preferentially derive from transcripts bearing miRNA response elements.
abstract: MHC I-associated peptides (MIPs) play an essential role in normal homeostasis and diverse pathologic conditions. MIPs derive mainly from defective ribosomal products (DRiPs), a subset of nascent proteins that fail to achieve a proper conformation and the physical nature of which remains elusive. In the present study, we used high-throughput proteomic and transcriptomic methods to unravel the structure and biogenesis of MIPs presented by HLA-A and HLA-B molecules on human EBV-infected B lymphocytes from 4 patients. We found that although HLA-different subjects present distinctive MIPs derived from different proteins, these MIPs originate from proteins that are functionally interconnected and implicated in similar biologic pathways. Secondly, the MIP repertoire of human B cells showed no bias toward conserved versus polymorphic genomic sequences, were derived preferentially from abundant transcripts, and conveyed to the cell surface a cell-type-specific signature. Finally, we discovered that MIPs derive preferentially from transcripts bearing miRNA response elements. Furthermore, whereas MIPs of HLA-disparate subjects are coded by different sets of transcripts, these transcripts are regulated by mostly similar miRNAs. Our data support an emerging model in which the generation of MIPs by a transcript depends on its abundance and DRiP rate, which is regulated to a large extent by miRNAs.
authors.affiliation: Institute for Research in Immunology and Cancer, Université deMontréal, Montréal, QC, Canada.
authors.forename: Diana Paola
authors.initials: DP
authors.lastname: Granados
authors.forename: Wafaa
authors.initials: W
authors.lastname: Yahyaoui
authors.forename: Céline M
authors.initials: CM
authors.lastname: Laumont
authors.forename: Tariq
authors.initials: T
authors.lastname: Daouda
authors.forename: Tara L
authors.initials: TL
authors.lastname: Muratore-Schroeder
authors.forename: Caroline
authors.initials: C
authors.lastname: Côté
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Laverdure
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lemieux
authors.forename: Pierre
authors.initials: P
authors.lastname: Thibault
authors.forename: Claude
authors.initials: C
authors.lastname: Perreault
mesh_terms: D017951:Antigen Presentation / Q000235:genetics* / Q000502:physiology; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D057809:HEK293 Cells; D015234:HLA-A Antigens / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D046228:Microarray Analysis; D008954:Models, Biological; D010455:Peptides / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000737:chemistry* / Q000235:genetics*; D020218:Response Elements / Q000235:genetics / Q000276:immunology*
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; D035683:MicroRNAs; D010455:Peptides; D012333:RNA, Messenger