1. Atomic structure of a human MHC molecule presenting an influenza virus peptide.
- Author
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Silver ML, Guo HC, Strominger JL, and Wiley DC
- Subjects
- Amino Acid Sequence, Binding Sites, HLA-B27 Antigen chemistry, Humans, Hydrogen Bonding, Models, Molecular, Molecular Sequence Data, Molecular Structure, Nucleoproteins metabolism, Peptide Fragments chemistry, Peptide Fragments metabolism, Protein Conformation, Receptors, Antigen, T-Cell metabolism, Viral Proteins metabolism, X-Ray Diffraction, HLA-A Antigens chemistry, Nucleoproteins chemistry, Orthomyxoviridae chemistry, Viral Proteins chemistry
- Abstract
Infection by influenza virus results in the stimulation of cytotoxic T lymphocytes specific for killing virally infected cells. 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 glycoproteins. 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 cryocrystallography. 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-B27. 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.
- Published
- 1992
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