Abstract
INFECTION by influenza virus results in the stimulation of cytotoxic T lymphocytes specific for killing virally infected cells1. Specificity is provided by clonally distributed, hypervariable T-cell receptors on cytotoxic T lymphocytes which react with peptide fragments that are derived from viral proteins expressed in the cytoplasm and 'presented' on the surface of infected cells, bound to class I histocompatibility glycoproteins2. Here we describe the structure of the complex between the human class I histocompatibility glycoprotein HLA-Aw68 and the influenza virus nucleoprotein peptide Np 91–99 as determined by X-ray cryo-crystallography. Residues at both ends of the peptide are substantially buried in the peptide binding-site, whereas those in the middle of the peptide, P4 to P8, are predominantly exposed and could be recognized directly by T-cell receptors. The extended conformation of the bound viral peptide is remarkably similar to that of a collection of endogenous peptides with a different sequence motif bound to another human allele, HLA-B273–5. The structure defines in atomic detail the antigenic surface constructed of major histocompatibility complex and viral peptide atoms that is recognized by T-cell receptors.
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Silver, M., Guo, HC., Strominger, J. et al. Atomic structure of a human MHC molecule presenting an influenza virus peptide. Nature 360, 367–369 (1992). https://doi.org/10.1038/360367a0
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DOI: https://doi.org/10.1038/360367a0
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