Identification of a superagonist variant of the immunodominant Yellow fever virus epitope NS4b <sub>214-222</sub> by combinatorial peptide library screening.

Details

Serval ID
serval:BIB_46FDF2862443
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Identification of a superagonist variant of the immunodominant Yellow fever virus epitope NS4b <sub>214-222</sub> by combinatorial peptide library screening.
Journal
Molecular immunology
Author(s)
Bovay A., Zoete V., Rizkallah P.J., Beck K., Delbreil P., Speiser D.E., Cole D.K., Fuertes Marraco S.A.
ISSN
1872-9142 (Electronic)
ISSN-L
0161-5890
Publication state
Published
Issued date
09/2020
Peer-reviewed
Oui
Volume
125
Pages
43-50
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The CD8 T cell response to the HLA-A2-restricted epitope LLWNGPMAV (LLW) of the non-structural protein 4b of Yellow Fever Virus (YFV) is remarkably immunodominant, highly prevalent and powerful in YFV-vaccinated humans. Here we used a combinatorial peptide library screening in the context of an A2/LLW-specific CD8 T cell clone to identify a superagonist that features a methionine to isoleucine substitution at position 7. Based on in silico modeling, the functional enhancement of this LLW-7I mutation was associated with alterations in the structural dynamics of the peptide in the major histocompatibility complex (pMHC) binding with the T cell receptor (TCR). While the TCR off-rate of LLW-7I pMHC is comparable to the wild type peptide, the rigidity of the 7I peptide seems to confer less entropy loss upon TCR binding. This LLW-7I superagonist is an example of improved functionality in human CD8 T cells associated with optimized ligand rigidity for TCR binding and not with changes in TCR:pMHC off-rate kinetics.
Keywords
CD8-Positive T-Lymphocytes/immunology, Epitopes, T-Lymphocyte/chemistry, Epitopes, T-Lymphocyte/immunology, HLA-A2 Antigen/chemistry, HLA-A2 Antigen/immunology, Humans, Immunodominant Epitopes/chemistry, Immunodominant Epitopes/immunology, Models, Molecular, Mutation, Peptide Library, Protein Binding/immunology, Receptors, Antigen, T-Cell/chemistry, Receptors, Antigen, T-Cell/immunology, Viral Nonstructural Proteins/immunology, Yellow fever virus/immunology, Altered peptide ligand, Antigen sensitivity, CD8 T cells, Peptide rigidity, Yellow fever virus
Pubmed
Web of science
Open Access
Yes
Create date
24/07/2020 11:44
Last modification date
22/10/2020 12:31
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