Analysis of Secondary Structure Biases in Naturally Presented HLA-I Ligands.

Details

Serval ID
serval:BIB_BA3DEC8F83B0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Analysis of Secondary Structure Biases in Naturally Presented HLA-I Ligands.
Journal
Frontiers in immunology
Author(s)
Perez MAS, Bassani-Sternberg M., Coukos G., Gfeller D., Zoete V.
ISSN
1664-3224 (Electronic)
ISSN-L
1664-3224
Publication state
Published
Issued date
2019
Peer-reviewed
Oui
Volume
10
Pages
2731
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Recent clinical developments in antitumor immunotherapy involving T-cell related therapeutics have led to a renewed interest for human leukocyte antigen class I (HLA-I) binding peptides, given their potential use as peptide vaccines. Databases of HLA-I binding peptides hold therefore information on therapeutic targets essential for understanding immunity. In this work, we use in depth and accurate HLA-I peptidomics datasets determined by mass-spectrometry (MS) and analyze properties of the HLA-I binding peptides with structure-based computational approaches. HLA-I binding peptides are studied grouping all alleles together or in allotype-specific contexts. We capitalize on the increasing number of structurally determined proteins to (1) map the 3D structure of HLA-I binding peptides into the source proteins for analyzing their secondary structure and solvent accessibility in the protein context, and (2) search for potential differences between these properties in HLA-I binding peptides and in a reference dataset of HLA-I motif-like peptides. This is performed by an in-house developed heuristic search that considers peptides across all the human proteome and converges to a collection of peptides that exhibit exactly the same motif as the HLA-I peptides. Our results, based on 9-mers matched to protein 3D structures, clearly show enriched sampling for HLA-I presentation of helical fragments in the source proteins. This enrichment is significant, as compared to 9-mer HLA-I motif-like peptides, and is not entirely explained by the helical propensity of the preferred residues in the HLA-I motifs. We give possible hypothesis for the secondary structure biases observed in HLA-I peptides. This contribution is of potential interest for researchers working in the field of antigen presentation and proteolysis. This knowledge refines the understanding of the rules governing antigen presentation and could be added to the parameters of the current peptide-MHC class I binding predictors to increase their antigen predictive ability.
Keywords
Amino Acid Motifs, Databases, Protein, Histocompatibility Antigens Class I/chemistry, Histocompatibility Antigens Class I/immunology, Humans, Ligands, Mass Spectrometry, Peptides/chemistry, Peptides/immunology, 3D structure, HLA-I ligand presentation, HLA-I motif-like peptides, computational immunology, heuristic search, human leukocyte antigen
Pubmed
Web of science
Open Access
Yes
Create date
15/12/2019 16:56
Last modification date
25/11/2020 6:25
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