title: Functional polymorphism of the KIR3DL1/S1 receptor on human NK cells.
abstract: NK cells express both inhibitory and activatory receptors that allow them to recognize target cells through HLA class I Ag expression. KIR3DL1 is a receptor that recognizes the HLA-Bw4 public epitope of HLA-B alleles. We demonstrate that polymorphism within the KIR3DL1 receptor has functional consequences in terms of NK cell recognition of target. Inhibitory alleles of KIR3DL1 differ in their ability to recognize HLA-Bw4 ligand, and a consistent hierarchy of ligand reactivity can be defined. KIR3DS1, which segregates as an allele of KIR3DL1, has a short cytoplasmic tail characteristic of activatory receptors. Because it is very similar to KIR3DL1 in the extracellular domains, it has been assumed that KIR3DS1 will recognize a HLA-Bw4 ligand. In this study, we demonstrate that KIR3DS1 is expressed as a protein at the cell surface of NK cells, where it is recognized by the Z27 Ab. Using this Ab, we found that KIR3DS1 is expressed on a higher percentage of NK cells in KIR3DS1 homozygous compared with heterozygous donors. In contrast to the inhibitory KIR3DL1 allotypes, KIR3DS1 did not recognize HLA-Bw4 on EBV-transformed cell lines.
authors.affiliation: School of Biochemistry and Immunology, Trinity College, Dublin, Ireland.
authors.forename: Geraldine M
authors.initials: GM
authors.lastname: O'Connor
authors.forename: Kieran J
authors.initials: KJ
authors.lastname: Guinan
authors.forename: Rodat T
authors.initials: RT
authors.lastname: Cunningham
authors.forename: Derek
authors.initials: D
authors.lastname: Middleton
authors.forename: Peter
authors.initials: P
authors.lastname: Parham
authors.forename: Clair M
authors.initials: CM
authors.lastname: Gardiner
mesh_terms: D000483:Alleles; D000906:Antibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D015235:HLA-B Antigens / Q000032:analysis / Q000276:immunology*; D004854:Herpesvirus 4, Human; D006801:Humans; D007694:Killer Cells, Natural / Q000737:chemistry / Q000276:immunology*; D011110:Polymorphism, Genetic; D011971:Receptors, Immunologic / Q000032:analysis / Q000235:genetics* / Q000276:immunology*; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1; D054349:Receptors, KIR3DS1
chemical_list: D000906:Antibodies; D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; C515083:KIR3DL1 protein, human; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1; D054349:Receptors, KIR3DS1