Response to Comment on “A subset of HLA-I peptides are not genomically templated: Evidence for cis- and trans-spliced peptide ligands”

Faridi, Pouya; Li, Chen; Ramarathinam, Sri H.; Illing, Patricia T.; Mifsud, Nicole A.; Ayala, Rochelle; Song, Jiangning; Gearing, Linden J.; Croft, Nathan P.; Purcell, Anthony W.

doi:10.1126/sciimmunol.aaw8457

Cited by 23 publications

(17 citation statements)

References 9 publications

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“…Methionine oxidation, deamidation (NQ), N-terminal acetylation and phosphorylation (STY) were set as variable PTMs. Although spliced peptides have been identified in cellular proteomes and immunopeptidomes ( Faridi et al., 2019 ; Liepe et al., 2016 , 2019 ; Mishto and Liepe 2017 ), they were not included in the analysis. Results were filtered for 1% FDR based on peptide spectrum matches (PSMs) using a target decoy approach with a randomized decoy database ( Table S2 ).…”

Section: Methodsmentioning

confidence: 99%

Identification of a class of non-conventional ER-stress-response-derived immunogenic peptides

et al. 2021

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Identification of a class of non-conventional ERstress-response-derived immunogenic peptidesGraphical abstract Highlights d Tumor cell infection with Salmonella induces the release of immunogenic peptides d Peptide-based vaccine boosts a strong antitumor response in dog osteosarcoma d MS analysis identified shared peptides released by human melanoma cell lines d Twelve identified peptides are capable of inducing a tumorspecific CD8 response

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Section: Methodsmentioning

confidence: 99%

Identification of a class of non-conventional ER-stress-response-derived immunogenic peptides

et al. 2021

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“…In addition to mRNA splicing, proteasomal splicing might also be a source of TSAs 93,94 , although their formation and frequency of occurrence currently remains controversial [95][96][97][98] . Basic characterizations of antigenic peptides produced by peptide splicing in the proteasome have already been conducted using cDNA-based approaches 51,99 .…”

Section: Wwwnaturecom/nrclinoncmentioning

confidence: 99%

Towards new horizons: characterization, classification and implications of the tumour antigenic repertoire

et al. 2020

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Immunologically recognizable cell-surface structures. Antigen-aware therapy (AaT). An active immunotherapy leading to the activation of and/or constituting antigenspecific cells designed to target known and/or well-defined antigens. Antigen-unaware therapy (AuT). An active immunotherapy leading to the activation of and/or constituting antigenspecific cells designed to targeting uncharacterized antigens.

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“…Putative spliced sequences reported by Liepe and colleagues [12,13] and us [7] have attracted considerable criticism, with others preferring to describe these species as unanticipated or alternative reading frames, highly chemically post‐translationally modified species or no explanation given at all [18,20,34,37–39]. One of the debates focuses upon other possible explanations for proposed spliced peptides.…”

Section: The Debate On the Existence Prevalence And Importance Of Spliced Peptidesmentioning

confidence: 99%

Spliced HLA-bound peptides: a Black Swan event in immunology

Faridi

Dorvash

Purcell

2021

Clinical and Experimental Immunology

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Peptides that bind to and are presented on the cell surface by human leucocyte antigen (HLA) molecules play a critical role in adaptive immunity. For a long time it was believed that all the HLA-bound peptides were generated through simple proteolysis of linear sequences of cellular proteins, and therefore are templated in the genome and proteome. However, evidence for untemplated peptide ligands of HLA molecules has accumulated during the last two decades, with a recent global analysis of HLA-bound peptides suggesting that a considerable proportion of HLAbound peptides are potentially generated through splicing/fusion of discontinuous peptide segments from one or two distinct proteins. In this review, we will evaluate recent discoveries and debates on the contribution of spliced peptides to the HLA class I immunopeptidome, consider biochemical rules for splicing and the potential role of these spliced peptides in immune recognition.

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Response to Comment on “A subset of HLA-I peptides are not genomically templated: Evidence for cis- and trans-spliced peptide ligands”

Abstract: This is our response to the Technical Comment by Rolfset al.where we point out errors in their reanalysis of our data.

Cited by 23 publications

References 9 publications

Identification of a class of non-conventional ER-stress-response-derived immunogenic peptides

Identification of a class of non-conventional ER-stress-response-derived immunogenic peptides

Towards new horizons: characterization, classification and implications of the tumour antigenic repertoire

Spliced HLA-bound peptides: a Black Swan event in immunology

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