Bovay, Amandine, Zoete, Vincent, Rizkallah, Pierre J ![]() ![]() ![]() ![]() |
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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.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Dentistry Medicine |
Publisher: | Elsevier |
ISSN: | 0161-5890 |
Date of First Compliant Deposit: | 9 July 2020 |
Date of Acceptance: | 24 June 2020 |
Last Modified: | 05 Jan 2024 08:11 |
URI: | https://orca.cardiff.ac.uk/id/eprint/133295 |
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