Proteomics

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SPI-ART and the features of cis-spliced peptides in HLA class I immunopeptidomes


ABSTRACT: The identification of peptides presented by HLA class I molecules to CD8+ T cells – i.e. the HLA-I immunopeptidome - is a useful tool to fish epitopes suitable for vaccinations and immunotherapies against cancer, infection and autoimmunity. These peptides are mainly generated by proteasomes through peptide hydrolysis and peptide splicing. Post-translationally spliced epitopes can enlarge the antigenic landscape and thus immunotherapy efficacy. Their identification is challenging, and the few methods proposed so far hinted toward a controversial broad spectrum of cis-spliced peptide frequencies in HLA-I immunopeptidomes. We here developed a new method named SPI-ART, which can identify cis-spliced peptides in HLA-I immunopeptidomes with precision and recall outperforming all other methods. The benchmark of the methods’ performances provided the proper analytical framework to explain the discordant results published so far. It also allowed to estimate the frequency of cis-spliced peptides in HLA-I immunopeptidomes, and to shed light on the biochemistry of these unconventional peptides and their potential antigenicity.

INSTRUMENT(S): Orbitrap Fusion Lumos, Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Michele Mishto  

LAB HEAD: Juliane Liepe

PROVIDER: PXD025346 | Pride | 2022-08-12

REPOSITORIES: Pride

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Synthetic peptides are commonly used in biomedical science for many applications in basic and translational research. While peptide synthesis is generally easy and reliable, the chemical nature of some amino acids as well as the many steps and chemical compounds involved can render the synthesis of some peptide sequences difficult. Identification of these problematic sequences and mitigation of issues they may present can be important for the reliable use of peptide reagents in several contexts.  ...[more]

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