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Updated: Jun 8, 2026
09:32
Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis
Published on: October 15, 2021
Two abundant proteasome subtypes that uniquely process some antigens presented by HLA class I molecules
Benoît Guillaume1, Jacques Chapiro, Vincent Stroobant
1Ludwig Institute for Cancer Research, Brussels Branch, 1200 Brussels, Belgium.
Summary
New research reveals intermediate proteasomes, containing some standard and some inducible subunits, are abundant in human tissues and tumors. These proteasomes influence the range of antigenic peptides presented, impacting CD8 T cell responses.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Antigenic peptides presented by MHC class I molecules originate from intracellular protein degradation by proteasomes.
- The standard proteasome can be replaced by the immunoproteasome in certain conditions, altering peptide repertoire.
- The existence of proteasomes with mixed standard and inducible subunits was previously suggested but not fully characterized.
Purpose of the Study:
- To isolate, quantify, and characterize intermediate human proteasomes containing a mix of standard and inducible catalytic subunits.
- To determine the prevalence of these intermediate proteasomes in various human tissues and cell types.
- To investigate the role of intermediate proteasomes in processing specific tumor antigens.
Main Methods:
- Utilized unique subunit-specific antibodies for the isolation and characterization of human proteasomes.
- Quantified the presence of intermediate proteasomes in different human tissues (liver, colon, small intestine, kidney) and cell types (tumor cells, dendritic cells).
- Identified and analyzed the processing of specific tumor antigens (MAGE-A3, MAGE-A10) by distinct intermediate proteasome forms.
Main Results:
- Successfully isolated and characterized intermediate proteasomes containing one (β5i) or two (β1i and β5i) inducible subunits.
- These intermediate proteasomes constitute a significant fraction (one-third to one-half) of proteasome content in several human organs.
- Identified two clinically relevant tumor antigens processed exclusively by specific intermediate proteasomes (β5i or β1i-β5i).
Conclusions:
- Intermediate proteasomes are a substantial component of the human proteasome pool in various tissues and cell types.
- The existence of intermediate proteasomes expands the repertoire of antigenic peptides presented to CD8 T cells.
- Cellular antigen presentation is significantly influenced by the specific composition of proteasome content.
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