Commentary: Are There Indeed Spliced Peptides in the Immunopeptidome?

Michele Mishto

doi:10.1016/j.mcpro.2021.100158

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.

Highlights

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. He suggests that proteasomes cannot efficiently catalyze such a reaction, and, 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
Despite a plethora of in cellula, ex vivo, and in vivo evidence supporting a sizeable presentation of spliced peptides to cytotoxic T lymphocyte (CTL), 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]

Summary

Introduction

Proteasome-generated spliced epitopes presented by HLA class I complexes are emerging targets for T cell targeted immunotherapies. 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].

Results

Conclusion