Atomic structure of a human MHC molecule presenting an influenza virus peptide.
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.
Silver
M L
ML
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts 02138.
Guo
H C
HC
Strominger
J L
JL
Wiley
D C
DC
D000595:Amino Acid Sequence; D001665:Binding Sites; D015234:HLA-A Antigens / Q000737:chemistry*; D015796:HLA-B27 Antigen / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009698:Nucleoproteins / Q000737:chemistry* / Q000378:metabolism; D009975:Orthomyxoviridae / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism; D014961:X-Ray Diffraction
D015234:HLA-A Antigens; C053029:HLA-A*68 antigen; D015796:HLA-B27 Antigen; D009698:Nucleoproteins; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D014764:Viral Proteins