Commentary: Are there indeed spliced peptides in the immunopeptidome?

Proteasome-generated spliced epitopes presented by HLA class I complexes are emerging targets for T cell targeted immunotherapies. Their identification by mass spectrometry triggered heated debates, which find a representative opinion in one of the two fronts in the recent perspective article by Arie Admon. Briefly, he suggests that proteasomes cannot efficiently catalyse such a reaction, and, thus, that all spliced peptides identified in HLA class I immunopeptidomes and other specimens are artefacts. This hypothesis is in contrast with in vitro, in cellula and in vivo results published since the discovery of proteasome-catalysed peptide splicing in 2004.