Are There Indeed Spliced Peptides in the Immunopeptidome?

Abstract

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The Functional and Mechanistic Roles of Immunoproteasome Subunits in Cancer

“…The biological relevance of these spliced peptides is still controversial. Further studies are needed to validate these findings that these epitopes do exist and are not the unclassified peptides from any novel posttranslational modification or generated from a non-canonical transcript [ 101 ].…”

Is the Immunopeptidome Getting Darker?: A Commentary on the Discussion around Mishto et al., 2019

“…The maturation of informatic approaches to handle this challenging data has also facilitated routine analysis of these non-tryptic peptides allowing thousands of confident identifications to be made. However, it is clear that there are still informatic challenges in the peptide-centric data analysis pipelines (12,13) with a much lower proportion of spectra confidently assigned from immunopeptidomics data compared with more conventional samples such as tryptic digests of cell lysates. The search to explain these dark elements of the immunopeptidome has driven differences in interpretation and peptide sequence assignments to these MS/MS spectra (12,(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25).…”

Commentary: Are There Indeed Spliced Peptides in the Immunopeptidome?

“…Indeed, after the initial studies on cis - and trans -spliced peptides in HLA-I immunopeptidomes ( 24 , 25 , 26 ), a barrage of contradicting studies has been published, leaving the community doubtful of the real relevance of spliced peptides in the immune response. A summary of these studies is reported in Admon’s perspective ( 23 ) published in this special issue, as well as other recent reviews ( 27 ). Admon ( 23 ), however, extends the narrative and “argued that peptide splicing is, at most, an extremely rare event and likely does not happen at all.” He based this claim on two main arguments.…”

“…Despite a plethora of in cellula , ex vivo , and in vivo evidence supporting a sizeable presentation of spliced peptides to CTLs, and an involvement of these unconventional peptides in the immune response, researchers in this field are arguing about the frequency of spliced peptides in HLA-I immunopeptidomes ( 21 , 22 , 23 ). Indeed, after the initial studies on cis - and trans -spliced peptides in HLA-I immunopeptidomes ( 24 , 25 , 26 ), a barrage of contradicting studies has been published, leaving the community doubtful of the real relevance of spliced peptides in the immune response.…”