title: Conserved and variable residues within the Bw4 motif of HLA-B make separable contributions to recognition by the NKB1 killer cell-inhibitory receptor.
abstract: Allotypes from four divergent HLA-B families (B8, B15, B16, and B27) were compared for their inhibition of cytolysis by NK cells expressing the NKB1 receptor. Allotypes differing solely at the Bw4/Bw6 region were examined as were a more divergent subset of B15 allotypes. The capacity to interact with NKB1 correlated precisely with possession of a Bw4 sequence motif at residues 77-83, whereas no correlation was made with the peptide-binding specificities of two Bw4 and four Bw6 allotypes of the B15 family. HLA-B allotypes having four different Bw4 motifs were examined and all interact with NKB1. In contrast, HLA-A allotypes, which have a Bw4 motif identical with one of those present in HLA-B, do not. Mutation at leucine 82 and arginine 83, the residues common to Bw4 motifs, shows they contribute to NKB1 interaction but are not essential. Three types of polymorphism are implicated in formation of the ligand recognized by NKB1: ones shared by Bw4 motifs; ones distinguishing Bw4 motifs; and ones outside the Bw4/Bw6 region that distinguish HLA-B from HLA-A.
authors.affiliation: Department of Microbiology and Immunology, Stanford University, CA 94305, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Gumperz
authors.forename: L D
authors.initials: LD
authors.lastname: Barber
authors.forename: N M
authors.initials: NM
authors.lastname: Valiante
authors.forename: L
authors.initials: L
authors.lastname: Percival
authors.forename: J H
authors.initials: JH
authors.lastname: Phillips
authors.forename: L L
authors.initials: LL
authors.lastname: Lanier
authors.forename: P
authors.initials: P
authors.lastname: Parham
mesh_terms: D001665:Binding Sites / Q000235:genetics; D002999:Clone Cells; D017124:Conserved Sequence; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology*; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1; D017421:Sequence Analysis
chemical_list: D015235:HLA-B Antigens; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1