Accurate MHC Motif Deconvolution of Immunopeptidomics Data Reveals a Significant Contribution of DRB3, 4 and 5 to the Total DR Immunopeptidome

Mass spectrometry (MS) based immunopeptidomics is used in several biomedical applications including neo-epitope discovery in oncology, next-generation vaccine development and protein-drug immunogenicity assessment. Immunopeptidome data are highly complex given the expression of multiple HLA alleles...

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Bibliographic Details
Published in:Frontiers in immunology 2022-01, Vol.13, p.835454-835454
Main Authors: Kaabinejadian, Saghar, Barra, Carolina, Alvarez, Bruno, Yari, Hooman, Hildebrand, William H, Nielsen, Morten
Format: Article
Language:English
Subjects:
Cell Line
Databases, Protein
DRB3/4/5
Epitopes, T-Lymphocyte - immunology
Histocompatibility Antigens Class I - immunology
Histocompatibility Antigens Class II - immunology
HLA-DR Antigens - immunology
Humans
Immunology
immunopeptidome
Ligands
Mass Spectrometry
MHC motif deconvolution
MHCMotifDecon
Peptides - metabolism
Protein Binding
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Summary:Mass spectrometry (MS) based immunopeptidomics is used in several biomedical applications including neo-epitope discovery in oncology, next-generation vaccine development and protein-drug immunogenicity assessment. Immunopeptidome data are highly complex given the expression of multiple HLA alleles on the cell membrane and presence of co-immunoprecipitated contaminants. The absence of tools that deal with these challenges effectively and guide the analysis and interpretation of this complex type of data is currently a major bottleneck for the large-scale application of this technique. To resolve this, we here present the MHCMotifDecon that benefits from state-of-the-art HLA class-I and class-II predictions to accurately deconvolute immunopeptidome datasets and assign individual ligands to the most likely HLA molecule, allowing to identify and characterize HLA binding motifs while discarding co-purified contaminants. We have benchmarked the tool against other state-of-the-art methods and illustrated its application on experimental datasets for HLA-DR demonstrating a previously underappreciated role for HLA-DRB3/4/5 molecules in defining HLA class II immune repertoires. With its ease of use, MHCMotifDecon can efficiently guide interpretation of immunopeptidome datasets, serving the discovery of novel T cell targets. MHCMotifDecon is available at https://services.healthtech.dtu.dk/service.php?MHCMotifDecon-1.0.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2022.835454