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Updated: Sep 27, 2025

Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis
Published on: October 15, 2021
MHC Class I Immunopeptidome: Past, Present, and Future.
1Cellular Biology Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
The immunopeptidome, peptides presented for immunosurveillance, has been extensively characterized over 35 years. Recent advances link it to the translatome, fueling a renaissance in antigen processing and T-cell cancer immunotherapy.
Area of Science:
- Immunology
- Molecular Biology
- Proteomics
Background:
- Major histocompatibility complex (MHC) class I and II molecules present short peptides, dictating T-cell recognition.
- Over 35 years, significant progress has been made in characterizing the immunopeptidome for immunosurveillance.
Purpose of the Study:
- To review major milestones in immunopeptidome characterization.
- To discuss the role of proteasome-mediated splicing in shaping the immunopeptidome.
- To detail recent findings connecting the immunopeptidome to the translatome via ribosome profiling (RiboSeq).
Main Methods:
- Review of historical milestones in immunopeptidome research.
- Discussion of proteasome-mediated splicing mechanisms.
- Integration of ribosome profiling (RiboSeq) data with immunopeptidome studies.
Main Results:
- Characterization of the immunopeptidome has advanced significantly.
- Proteasome-mediated splicing contributes to the immunopeptidome.
- Emerging links between the immunopeptidome and the translatome (RiboSeq) are identified.
Conclusions:
- The field of antigen processing is experiencing a renaissance.
- Continued progress requires new talent and integration of advanced techniques.
- T-cell-based cancer immunotherapy success drives interest in immunopeptidome research.
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