Commentary: Are There Indeed Spliced Peptides in the Immunopeptidome?

Abstract

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 catalyze such a reaction, and, thus, that all spliced peptides identified in HLA class I immunopeptidomes and other specimens are artifacts. This hypothesis is in contrast with in vitro, in cellula, and in vivo results published since the discovery of proteasome-catalyzed peptide splicing in 2004.

Keywords: HLA class I; Proteasomes; T cell response; epitopes; in vitro digestions; mass spectrometry; peptide splicing; proteomics.