1. HLA-B and cysteinylated ligands distinguish the antigen presentation landscape of extracellular vesicles.
- Author
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Bauzá-Martinez J, Heck AJR, and Wu W
- Subjects
- Cell Line, Chromatography, Liquid methods, Cysteine metabolism, Extracellular Vesicles metabolism, HLA-B Antigens metabolism, Humans, Ligands, Peptides immunology, Peptides metabolism, Protein Processing, Post-Translational immunology, Proteomics methods, Tandem Mass Spectrometry methods, Antigen Presentation immunology, Cysteine immunology, Extracellular Vesicles immunology, HLA-B Antigens immunology
- Abstract
Extracellular vesicles can modulate diverse processes ranging from proliferation and tissue repair, to chemo-resistance and cellular differentiation. With the advent of tissue and immunological targeting, extracellular vesicles are also increasingly viewed as promising vectors to deliver peptide-based cancer antigens to the human immune system. Despite the clinical relevance and therapeutic potential of such 'cell-free' approaches, the natural antigen presentation landscape exported in extracellular vesicles is still largely uncharted, due to the challenging nature of such preparations and analyses. In the context of therapeutic vesicle production, a critical evaluation of the similarity in vesicular antigen presentation is also urgently needed. In this work, we compared the HLA-I peptide ligandomes of extracellular vesicles against that of whole-cells of the same cell line. We found that extracellular vesicles not only over-represent HLA-B complexes and peptide ligands, but also cysteinylated peptides that may modulate immune responses. Collectively, these findings describe the pre-existing provision of vesicular HLA complexes that may be utilized to carry peptide vaccines, as well as the propensity for different peptide and post-translationally modified ligands to be presented, and will outline critical considerations in devising novel EV vaccination strategies.
- Published
- 2021
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