6SS8

Human Leukocyte Antigen Class I A02 Carrying LLWNGPIAV

Summary for 6SS8

• Entry DOI: 10.2210/pdb6ss8/pdb
• Descriptor: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, LEU-LEU-TRP-ASN-GLY-PRO-ILE-ALA-VAL, ... (9 entities in total)
• Functional Keywords: yellow fever, altered peptide ligand, human major histocompatibility complex, x-ray 3d structure determination, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 91947.77

Authors

Rizkallah, P.J.,Bovay, A. (deposition date: 2019-09-06, release date: 2020-07-15, Last modification date: 2024-10-09)

Primary citation

Bovay, A.,Zoete, V.,Rizkallah, P.J.,Beck, K.,Delbreil, P.,Speiser, D.E.,Cole, D.K.,Fuertes Marraco, S.A.
Identification of a superagonist variant of the immunodominant Yellow fever virus epitope NS4b214-222by combinatorial peptide library screening.
Mol.Immunol., 125:43-50, 2020

PubMed 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.

PubMed: 32645549
DOI: 10.1016/j.molimm.2020.06.025

Experimental method

X-RAY DIFFRACTION (2.24 Å)