title: Nonstandard peptide binding revealed by crystal structures of HLA-B*5101 complexed with HIV immunodominant epitopes.
abstract: The crystal structures of the human MHC class I allele HLA-B*5101 in complex with 8-mer, TAFTIPSI, and 9-mer, LPPVVAKEI, immunodominant peptide epitopes from HIV-1 have been determined by x-ray crystallography. In both complexes, the hydrogen-bonding network in the N-terminal anchor (P1) pocket is rearranged as a result of the replacement of the standard tyrosine with histidine at position 171. This results in a nonstandard positioning of the peptide N terminus, which is recognized by B*5101-restricted T cell clones. Unexpectedly, the P5 peptide residues appear to act as anchors, drawing the peptides unusually deeply into the peptide-binding groove of B51. The unique characteristics of P1 and P5 are likely to be responsible for the zig-zag conformation of the 9-mer peptide and the slow assembly of B*5101. A comparison of the surface characteristics in the alpha1-helix C-terminal region for B51 and other MHC class I alleles highlights mainly electrostatic differences that may be important in determining the specificity of human killer cell Ig-like receptor binding.
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, Oxford, United Kingdom. kmaenaka@lab.nig.ac.uk
authors.forename: K
authors.initials: K
authors.lastname: Maenaka
authors.forename: T
authors.initials: T
authors.lastname: Maenaka
authors.forename: H
authors.initials: H
authors.lastname: Tomiyama
authors.forename: M
authors.initials: M
authors.lastname: Takiguchi
authors.forename: D I
authors.initials: DI
authors.lastname: Stuart
authors.forename: E Y
authors.initials: EY
authors.lastname: Jones
mesh_terms: D020816:Amino Acid Motifs / Q000276:immunology; D000818:Animals; D001665:Binding Sites / Q000276:immunology; D002460:Cell Line; D003198:Computer Simulation; D003429:Cross Reactions; D018360:Crystallography, X-Ray; D003601:Cytotoxicity Tests, Immunologic; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D015235:HLA-B Antigens / Q000737:chemistry* / Q000378:metabolism; D059949:HLA-B51 Antigen; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D046911:Macromolecular Substances; D051379:Mice; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D011487:Protein Conformation; D011971:Receptors, Immunologic / Q000737:chemistry / Q000378:metabolism; D054340:Receptors, KIR; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
chemical_list: D015235:HLA-B Antigens; D059949:HLA-B51 Antigen; D016056:Immunodominant Epitopes; D046911:Macromolecular Substances; D010446:Peptide Fragments; D011971:Receptors, Immunologic; D054340:Receptors, KIR