Functional inhibitory human leucocyte antigen class I receptors on natural killer (NK) cells in patients with chronic NK lymphocytosis.
Chronic natural killer (NK) lymphocytosis is a rare disorder characterized by an indolent clinical course. Despite high NK cell numbers, many patients present with only mild clinical symptoms, and are often asymptomatic. NK cells are equipped with a range of receptors that bind human leucocyte antigen (HLA)-class I molecules. The killer immunoglobulin-like receptors (KIR, CD158) bind groups of HLA alleles, the CD94/NKG2 receptors bind HLA-E, and the CD85j (ILT2, LIR-1) receptor binds to the relatively non-polymorphic alpha3 domain of HLA molecules. Inhibitory HLA class I receptors silence NK cells against cells expressing normal levels of HLA class I. Analysis of NK cells in six patients with chronic NK lymphocytosis revealed a high level of the inhibitory CD94/NKG2A receptor on all NK cells. In four patients, KIR were absent, in one patient a single KIR was expressed in the absence of self-ligand, and in one patient CD85j and multiple KIR were expressed. Cytotoxicity assays demonstrated that all HLA class I receptors were functional. The ability of monoclonal antibodies to block the receptors and allow killing of autologous target cells established that both receptor and ligand expression were adequate for inhibitory function. We propose that the silent behaviour of NK cells in patients with chronic NK lymphocytosis is due to effective inhibitory HLA class I receptors.
Warren
Hilary S
HS
Division of Immunology and Genetics, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia. Hilary.Warren@anu.edu.au
Christiansen
Frank T
FT
Witt
Campbell S
CS
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D002908:Chronic Disease; D005260:Female; D005838:Genotype; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000378:metabolism; D008218:Lymphocytosis / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D017452:Receptors, IgG / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D055607:Receptors, Natural Killer Cell
D015703:Antigens, CD; D015395:Histocompatibility Antigens Class I; C527054:KLRC1 protein, human; C497869:KLRD1 protein, human; D037181:Lectins, C-Type; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell