A multigene family on human chromosome 12 encodes natural killer-cell lectins

Abstract

We previously isolated a series of cDNA clones designated NKG2-A, B, C, and D from a human natural killer (NK) cell library. These transcripts encode a family of type II integral membrane proteins having an extracellular Ca(2+)-dependent lectin domain. The predicted peptides share structural similarities and amino acid sequence similarity with known receptor molecules. In this report, the genomic organization and mRNA expression of each of the genes were studied by using transcript-specific probes. Southern blot experiments reveal that the probes cross-hybridize with a maximum of five genes at high stringency. By probing a Southern blot prepared from a series of hamster/human hybrid somatic cell lines, we demonstrated that all of the hybridizing fragments occur on human chromosome 12. No gene rearrangement and little restriction fragment length polymorphism (RFLP) was observed with these probes. mRNA expression of the NKG2 genes occurred in NK cells and some T cells but not in other hematopoietic cell types or in other tissues tested. Each of the transcripts occurred in all three of the NK cell lines tested: however, the genes were differentially regulated in T cells. NKG2-D was expressed in nine of fourteen T-cell clones or lines in the panel, whereas NKG2-A/B was expressed in three and NKG2-C was expressed in only one. Expression of each of the transcripts was upregulated following T-cell growth factor (TCGF)-induced activation of a cloned NK cell. The limited distribution of these proteins and their sequence similarity with known receptor molecules suggest that they may function as receptors on human NK cells.

AICL: a new activation-induced antigen encoded by the human NK gene complex

“…Since the genes encoding NKG2, NKR-P1A, and CD94 were also mapped to chromosome 12 (Yabe et al 1993;Lanier et al 1994;Chang et al 1995), we expected that the AICL gene would be localized there. Therefore, an STS-based YAC contig map of chromosome 12 (Krauter et al 1995) was screened.…”

Differential Cytokine Responses following Marek's Disease Virus Infection of Chickens Differing in Resistance to Marek's Disease

“…MD resistance in these lines has been mapped to genetic loci outside of the MHC, most importantly a cluster of genes (MDV1 locus) on chicken chromosome 1 (9). This region has synteny with the mammalian lectin-like natural killer (NK) cell antigen complex (31,65) that contains the Cmv1 locus for resistance to murine cytomegalovirus (8,33,47). The outcome of MDV infection is associated with MDV load during the early stages of infection, a significant association between viral load in peripheral blood leukocytes and the development of clinical MD being evident as early as 4 dpi (10).…”

The NKG2 natural killer cell receptor family: comparative analysis of promoter sequences

“…19 Expression of NKG2 genes is limited to NK cells and a subset of cytotoxic T-cells (Tc). 20 Individual NKG2 members can be expressed separately or in combinations on NK as well as Tc subsets, 12 a process which seems to be regulated transcriptionally and is thus reflected in mRNA expression. 20 Development of an NK-like phenotype, ie, de novo expression of CD94/NKG2-A can be induced by cytokines such as IL-2, IL-15 and TGF-␤ on immature thymocytes or Tc subsets.…”

“…20 Individual NKG2 members can be expressed separately or in combinations on NK as well as Tc subsets, 12 a process which seems to be regulated transcriptionally and is thus reflected in mRNA expression. 20 Development of an NK-like phenotype, ie, de novo expression of CD94/NKG2-A can be induced by cytokines such as IL-2, IL-15 and TGF-␤ on immature thymocytes or Tc subsets. 21,22 NKG2 mRNA levels can be further increased by prolonged treatment of NK cells with IL-2 or IFN-␣, thus pointing to further regulation at the transcriptional level.…”

“…21,22 NKG2 mRNA levels can be further increased by prolonged treatment of NK cells with IL-2 or IFN-␣, thus pointing to further regulation at the transcriptional level. 20,23 However, to date little is known about the promoter regions of NKG2 genes, which should harbor various regulatory elements mediating cell type-specific expression as well as cytokine responsiveness.…”