Solving an MHC allele-specific bias in the reported immunopeptidome Journal Article
| Authors: | Klatt, M. G.; Mack, K. N.; Bai, Y.; Aretz, Z. E. H.; Nathan, L. I.; Mun, S. S.; Dao, T.; Scheinberg, D. A. |
| Article Title: | Solving an MHC allele-specific bias in the reported immunopeptidome |
| Abstract: | Identification of MHC class I-bound peptides by immunopurification of MHC complexes and subsequent analysis by mass spectrometry is crucial for understanding T cell immunology and immunotherapy. Investigation of the steps for the MHC ligand isolation process revealed biases in widely used isolation techniques toward peptides of lower hydrophobicity. As MHC ligand hydrophobicity correlates positively with immunogenicity, identification of more hydrophobic MHC ligands could potentially lead to more effective isolation of immunogenic peptides as targets for immunotherapies. We solved this problem by use of higher concentrations of acetonitrile for the separation of MHC ligands and their respective complexes. This increased overall MHC ligand identifications by 2-fold, increased detection of cancer germline antigen-derived peptides by 50%, and resulted in profound variations in isolation efficacy between different MHC alleles correlating with the hydrophobicity of their anchor residues. Overall, these insights enabled a more complete view of the immunopeptidome and overcame a systematic underrepresentation of these critical MHC ligands of high hydrophobicity. |
| Keywords: | antigen presentation; immunology; immunotherapy; mhc class 1 |
| Journal Title: | JCI Insight |
| Volume: | 5 |
| Issue: | 19 |
| ISSN: | 2379-3708 |
| Publisher: | Amer Soc Clinical Investigation Inc |
| Date Published: | 2020-10-02 |
| Start Page: | e141264 |
| Language: | English |
| DOI: | 10.1172/jci.insight.141264 |
| PUBMED: | 32897882 |
| PROVIDER: | scopus |
| PMCID: | PMC7566711 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 November 2020 -- Source: Scopus |
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