| Autor: |
Amandine, Bovay, Vincent, Zoete, Pierre J, Rizkallah, Konrad, Beck, Philippe, Delbreil, Daniel E, Speiser, David K, Cole, Silvia A, Fuertes Marraco |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
Molecular immunology. 125 |
| ISSN: |
1872-9142 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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