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 HISTOCOMPATIBILITY COMPLEX HAPLOTYPE

Natural killer (NK) cells that express the NKB1 receptor are inhibited from killing target cells that possess human histocompatibility leuko cyte antigen (HLA) B molecules bearing the Bw4 serological epitope. To investigate whether NKB1 expression is affected by HLA type, peripher al blood lymphocytes of 203 HLA-typed donors were examined. Most donor s had a single population of NKB1(+), cells, but some had two populati ons expressing different cell surface levels of NKB1, and others had n o detectable NKB1(+) cells. Among the donors expressing NKB1, both the relative abundance of NKB1(+) NK cells and their level of cell surfac e expression varied substantially. The percentage of NKB1(+) NK cells ranged from 0 to >75% (mean 14.7%), and the mean fluorescence of the p ositive population varied over three orders of magnitude. For each don or, the small percentage of T cells expressing NKB1 (usually <2%), had a pattern of expression mirroring that of the NK cells. NKB1 expressi on by NK and T cells remained stable over thr 2-yr period that live do nors were tested. Patterns of NKB1 expression were not associated with Bw4 or Bw6 serotype of the donor or with the presence of any individu al HLA-A or -B antigens. Cells expressing NKB1 are often found in dono rs who do not possess an appropriate class I ligand, and can be absent in those who express Bw4(+) HLA-B antigens. Family studies further su ggested that the phenotype of NKB1 expression is inherited but not HLA linked. Whereas identical twins show matching patterns of NKB1 expres sion, HLA-identical siblings can differ in NKB1 expression and convers ely, HLA-disparate siblings can be similar. Thus NKB1 expression pheno types are tightly regulated and extremely heterogenous, but not correl ated with HLA type.