Innovations Toward Immunopeptidomics
- PMID: 39095021
- PMCID: PMC11419911
- DOI: 10.1016/j.mcpro.2024.100823
Innovations Toward Immunopeptidomics
Abstract
Over the past 30 years, immunopeptidomics has grown alongside improvements in mass spectrometry technology, genomics, transcriptomics, T cell receptor sequencing, and immunological assays to identify and characterize the targets of activated T cells. Together, multiple research groups with expertise in immunology, biochemistry, chemistry, and peptide mass spectrometry have come together to enable the isolation and sequence identification of endogenous major histocompatibility complex (MHC)-bound peptides. The idea to apply highly sensitive mass spectrometry techniques to study the landscape of peptide antigens presented by cell surface MHCs was innovative and continues to be successfully used and improved upon to deepen our understanding of how peptide antigens are processed and presented to T cells. Multiple research groups were involved in this bringing immunopeptidomics to the forefront of translational research, and we will highlight the contributions of one of the earliest developers, Professor Donald F. Hunt, and his research group at the University of Virginia. The Hunt laboratory applied cutting edge mass spectroscopy-based immunopeptidomics to study cancer, autoimmunity, transplant rejection, and infectious diseases. Across these diverse research areas, the Hunt laboratory and collaborators would characterize previously unknown MHC peptide-binding motifs and identify immunologically active antigens using ultra sensitive mass spectrometry techniques. Amazingly, many of the MHC-bound peptide antigens discovered in collaborations with the Hunt laboratory were sequenced by mass spectrometry before the completion of the human genome using manual de novo sequencing. In this perspective article, we will chronicle the work of the Hunt laboratory and their many collaborators that would be a major part of the foundation for mass spectrometry-based immunopeptidomics and its application to immunology research.
Keywords: HLA; MHC; antigen; immunopeptidomics; peptidomics.
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Conflict of interest J. G. A. is a paid consultant of Enara Bio. The other author declares no competing interests.
Figures


References
-
- Bjorkman P.J., Saper M.A., Samraoui B., Bennett W.S., Strominger J.L., Wiley D.C. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature. 1987;329:512–518. - PubMed
-
- Townsend A.R., Rothbard J., Gotch F.M., Bahadur G., Wraith D., McMichael A.J. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell. 1986;44:959–968. - PubMed
-
- Wabuke-Bunoti M.A., Fan D.P. Isolation and characterization of a CNBr cleavage peptide of influenza viral hemagglutinin stimulatory for mouse cytolytic T lymphocytes. J. Immunol. 1983;130:2386–2391. - PubMed
-
- Wabuke-Bunoti M.A., Taku A., Garman R., Fan D.P. Stimulation of anti-influenza cytolytic T lymphocytes by a synthetic peptide of the influenza hemagglutinin can be modulated by at least three independent helper factors. J. Immunol. 1984;133:2186–2193. - PubMed
-
- Guertin D.P., Fan D.P. Stimulation of cytolytic T cells by isolated viral peptides and HN protein coupled to agarose beads. Nature. 1980;283:308–311. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous