Deciphering the HLA-E immunopeptidome with mass spectrometry: an opportunity for universal mRNA vaccines and T-cell-directed immunotherapies

TL;DR

This paper explores how HLA-E molecules present peptides that could be used for universal vaccines and immunotherapies, using mass spectrometry to study their potential in treating infections and cancer.

Contribution

The paper introduces recent mass spectrometry methods for profiling HLA-E peptides, highlighting their potential as targets for broad-spectrum immunotherapies.

Findings

HLA-E presents pathogen-derived and tumor-associated peptides to CD8+ T cells.

MS technologies are advancing the profiling of HLA-E immunopeptidomes in various diseases.

HLA-E's monomorphic nature makes it a promising target for universal immunotherapies.

Abstract

Advances in immunotherapy rely on targeting novel cell surface antigens, including therapeutically relevant peptide fragments presented by HLA molecules, collectively known as the actionable immunopeptidome. Although the immunopeptidome of classical HLA molecules is extensively studied, exploration of the peptide repertoire presented by non-classical HLA-E remains limited. Growing evidence suggests that HLA-E molecules present pathogen-derived and tumor-associated peptides to CD8+ T cells, positioning them as promising targets for universal immunotherapies due to their minimal polymorphism. This mini-review highlights recent developments in mass spectrometry (MS) technologies for profiling the HLA-E immunopeptidome in various diseases. We discuss the unique features of HLA-E, its expression patterns, stability, and the potential for identifying new therapeutic targets. Understanding the broad repertoire of actionable peptides presented by HLA-E can lead to innovative treatments for viral and pathogen infections and cancer, leveraging its monomorphic nature for broad therapeutic efficacy.

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