title: Structural features impose tight peptide binding specificity in the nonclassical MHC molecule HLA-E.
abstract: The crystal structure of the nonclassical human class lb MHC molecule HLA-E has been determined in complex with a prototypic ligand, the nonamer peptide (VMAPRTVLL), derived from the highly conserved residues 3-11 of the human MHC class la leader sequence. The mode of peptide binding retains some of the standard features observed in MHC class la complexes, but novel features imply that HLA-E has evolved to mediate specific binding to a tightly defined set of almost identical hydrophobic peptides from the highly conserved class l leader sequences. These molecular adaptations make HLA-E a rigorous checkpoint at the cell surface reporting on the integrity of the antigen processing pathway to CD94/NKG2 receptor-bearing natural killer cells.
authors.affiliation: Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom.
authors.forename: C A
authors.initials: CA
authors.lastname: O'Callaghan
authors.forename: J
authors.initials: J
authors.lastname: Tormo
authors.forename: B E
authors.initials: BE
authors.lastname: Willcox
authors.forename: V M
authors.initials: VM
authors.lastname: Braud
authors.forename: B K
authors.initials: BK
authors.lastname: Jakobsen
authors.forename: D I
authors.initials: DI
authors.lastname: Stuart
authors.forename: A J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: J I
authors.initials: JI
authors.lastname: Bell
authors.forename: E Y
authors.initials: EY
authors.lastname: Jones
mesh_terms: D003461:Crystallography; D006680:HLA Antigens / Q000737:chemistry* / Q000378:metabolism*; D015795:HLA-B8 Antigen / Q000737:chemistry; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D010446:Peptide Fragments / Q000737:chemistry; D011485:Protein Binding / Q000276:immunology; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D000097625:HLA-E Antigens
chemical_list: D006680:HLA Antigens; D015795:HLA-B8 Antigen; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D000097625:HLA-E Antigens