title: Heterogeneous phenotypes of expression of the NKB1 natural killer cell class I receptor among individuals of different human histocompatibility leukocyte antigens types appear genetically regulated, but not linked to major histocompatibililty complex haplotype.
abstract: Natural killer (NK) cells that express the NKB1 receptor are inhibited from killing target cells that possess human histocompatibility leukocyte antigen (HLA) B molecules bearing the Bw4 serological epitope. To investigate whether NKB1 expression is affected by HLA type, peripheral blood lymphocytes of 203 HLA-typed donors were examined. Most donors had a single population of NKB1+ cells, but some had two populations expressing different cell surface levels of NKB1, and others had no detectable NKB1+ cells. Among the donors expressing NKB1, both the relative abundance of NKB1+ NK cells and their level of cell surface expression varied substantially. The percentage of NKB1+ NK cells ranged from 0 to >75% (mean 14.7%), and the mean fluorescence of the positive population varied over three orders of magnitude. For each donor, the small percentage of T cells expressing NKB1 (usually <2%), had a pattern of expression mirroring that of the NK cells. NKB1 expression by NK and T cells remained stable over the 2-yr period that five donors were tested. Patterns of NKB1 expression were not associated with Bw4 or Bw6 serotype of the donor or with the presence of any individual HLA-A or -B antigens. Cells expressing NKB1 are often found in donors who do not possess an appropriate class I ligand, and can be absent in those who express Bw4+ HLA-B antigens. Family studies further suggested that the phenotype of NKB1 expression is inherited but not HLA linked. Whereas identical twins show matching patterns of NKB1 expression, HLA-identical siblings can differ in NKB1 expression, and conversely, HLA-disparate siblings can be similar. Thus NKB1 expression phenotypes are tightly regulated and extremely heterogeneous, but not correlated with HLA type.
authors.affiliation: Department of Microbiology, Stanford University, California 94305, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Gumperz
authors.forename: N M
authors.initials: NM
authors.lastname: Valiante
authors.forename: P
authors.initials: P
authors.lastname: Parham
authors.forename: L L
authors.initials: LL
authors.lastname: Lanier
authors.forename: D
authors.initials: D
authors.lastname: Tyan
mesh_terms: D002999:Clone Cells; D005786:Gene Expression Regulation; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D006680:HLA Antigens / Q000235:genetics*; D015235:HLA-B Antigens / Q000032:analysis; D006239:Haplotypes; D006650:Histocompatibility Testing; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D011971:Receptors, Immunologic / Q000235:genetics*; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1
chemical_list: D006680:HLA Antigens; D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; C038652:HLA-Bw6 antigen; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1