PMID- 31824508
OWN - NLM
STAT- MEDLINE
DCOM- 20201106
LR  - 20201106
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 10
DP  - 2019
TI  - Analysis of Secondary Structure Biases in Naturally Presented HLA-I Ligands.
PG  - 2731
LID - 10.3389/fimmu.2019.02731 [doi]
LID - 2731
AB  - 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.
CI  - Copyright (c) 2019 Perez, Bassani-Sternberg, Coukos, Gfeller and Zoete.
FAU - Perez, Marta A S
AU  - Perez MAS
AD  - Computer-Aided Molecular Engineering, Department of Oncology, Ludwig Institute 
      for Cancer Research, University of Lausanne, Lausanne, Switzerland.
AD  - Swiss Institute of Bioinformatics, Lausanne, Switzerland.
FAU - Bassani-Sternberg, Michal
AU  - Bassani-Sternberg M
AD  - Human Integrated Tumor Immunology Discovery Engine, Department of Oncology, 
      Ludwig Institute for Cancer Research, University Hospital of Lausanne, Lausanne, 
      Switzerland.
FAU - Coukos, George
AU  - Coukos G
AD  - Human Integrated Tumor Immunology Discovery Engine, Department of Oncology, 
      Ludwig Institute for Cancer Research, University Hospital of Lausanne, Lausanne, 
      Switzerland.
FAU - Gfeller, David
AU  - Gfeller D
AD  - Swiss Institute of Bioinformatics, Lausanne, Switzerland.
AD  - Computational Cancer Biology, Department of Oncology, Ludwig Institute for Cancer 
      Research, University of Lausanne, Lausanne, Switzerland.
FAU - Zoete, Vincent
AU  - Zoete V
AD  - Computer-Aided Molecular Engineering, Department of Oncology, Ludwig Institute 
      for Cancer Research, University of Lausanne, Lausanne, Switzerland.
AD  - Swiss Institute of Bioinformatics, Lausanne, Switzerland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191122
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Ligands)
RN  - 0 (Peptides)
SB  - IM
MH  - Amino Acid Motifs
MH  - *Databases, Protein
MH  - Histocompatibility Antigens Class I/*chemistry/immunology
MH  - Humans
MH  - Ligands
MH  - Mass Spectrometry
MH  - Peptides/*chemistry/immunology
PMC - PMC6883762
OTO - NOTNLM
OT  - 3D structure
OT  - HLA-I ligand presentation
OT  - HLA-I motif-like peptides
OT  - computational immunology
OT  - heuristic search
OT  - human leukocyte antigen
EDAT- 2019/12/12 06:00
MHDA- 2020/11/11 06:00
PMCR- 2019/01/01
CRDT- 2019/12/12 06:00
PHST- 2019/02/18 00:00 [received]
PHST- 2019/11/07 00:00 [accepted]
PHST- 2019/12/12 06:00 [entrez]
PHST- 2019/12/12 06:00 [pubmed]
PHST- 2020/11/11 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2019.02731 [doi]
PST - epublish
SO  - Front Immunol. 2019 Nov 22;10:2731. doi: 10.3389/fimmu.2019.02731. eCollection 
      2019.