title: Definition of polymorphic residues on killer Ig-like receptor proteins which contribute to the HLA-C binding site.
abstract: Killer cell immunoglobulin-like receptors (KIR) bind HLA class I proteins in an allele- and locus-specific manner. This report describes the use of transfectants expressing recombinant chimeric proteins, comprising the extracellular portions of KIR molecules and the transmembrane and cytoplasmic tails of CD3-zeta, to create an in vitro system in which signaling is readily measured and that preserves the specificity of the KIR / HLA-C interaction. The identity of the amino acid residues on the KIR molecule important for binding to the HLA protein is not well understood; although some KIR2D residues involved in HLA-C recognition have been identified, their relative importance and whether other amino acids contribute to binding was unclear. This novel system was used to study, by site-directed mutagenesis, the role of various amino acids in KIR binding to HLA-C ligand. The data presented here show that while multiple polymorphic residues contribute to the HLA-C binding site on KIR proteins, two clusters of polymorphic residues define the group allotype specificity of HLA-C binding to a KIR2D molecule.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: J
authors.initials: J
authors.lastname: Richardson
authors.forename: H T
authors.initials: HT
authors.lastname: Reyburn
authors.forename: I
authors.initials: I
authors.lastname: Luque
authors.forename: M
authors.initials: M
authors.lastname: Valés-Gómez
authors.forename: J L
authors.initials: JL
authors.lastname: Strominger
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D015236:HLA-C Antigens / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D011110:Polymorphism, Genetic; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*
chemical_list: D017252:CD3 Complex; D015236:HLA-C Antigens; D011971:Receptors, Immunologic