The Length Distribution and Multiple Specificity of Naturally Presented HLA-I Ligands.

Details

Serval ID
serval:BIB_7CB706F40FEB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The Length Distribution and Multiple Specificity of Naturally Presented HLA-I Ligands.
Journal
Journal of immunology
Author(s)
Gfeller D., Guillaume P., Michaux J., Pak H.S., Daniel R.T., Racle J., Coukos G., Bassani-Sternberg M.
ISSN
1550-6606 (Electronic)
ISSN-L
0022-1767
Publication state
Published
Issued date
15/12/2018
Peer-reviewed
Oui
Volume
201
Number
12
Pages
3705-3716
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
HLA-I molecules bind short peptides and present them for recognition by CD8 <sup>+</sup> T cells. The length of HLA-I ligands typically ranges from 8 to 12 aa, but variability is observed across different HLA-I alleles. In this study we collected recent in-depth HLA peptidomics data, including 12 newly generated HLA peptidomes (31,896 unique peptides) from human meningioma samples, to analyze the peptide length distribution and multiple specificity across 84 different HLA-I alleles. We observed a clear clustering of HLA-I alleles with distinct peptide length distributions, which enabled us to study the structural basis of peptide length distributions and predict peptide length distributions from HLA-I sequences. We further identified multiple specificity in several HLA-I molecules and validated these observations with binding assays. Explicitly modeling peptide length distribution and multiple specificity improved predictions of naturally presented HLA-I ligands, as demonstrated in an independent benchmarking based on the new human meningioma samples.
Keywords
Alleles, Antigen Presentation, Antigens/genetics, Antigens/metabolism, CD8-Positive T-Lymphocytes/immunology, Computational Biology, Epitopes, T-Lymphocyte/genetics, Epitopes, T-Lymphocyte/metabolism, HLA Antigens/metabolism, Histocompatibility Antigens Class I/metabolism, Humans, Immunity, Cellular, Immunodominant Epitopes/genetics, Immunodominant Epitopes/metabolism, Ligands, Meningioma/immunology, Models, Chemical, Peptides/genetics, Peptides/metabolism, Polymorphism, Genetic, Protein Binding, T-Cell Antigen Receptor Specificity
Pubmed
Web of science
Create date
19/11/2018 13:22
Last modification date
20/08/2019 14:38
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