The centromeric part of the human NK gene complex: linkage of LOX-1 and LY49L with the CD94/NKG2 region

Abstract

The natural killer (NK) gene complex is a genomic region containing lectin-type receptor genes. We have established a contig of PAC and BAC clones comprising about 1 Mb of the centromeric part of the NK gene complex. This region extends from the LOX-1 gene, which encodes a receptor for oxidized LDL and was found within 100 kb telomeric of the STS marker D12S77, contains the CD94 and NKG2 NK receptor genes and reaches beyond D12S852 on the proximal side. In this part we have mapped the human LY49L gene, a homologue of the rodent Ly49 genes, which encode important MHC class I receptors for the regulation of NK cell activity in rodents. The LY49L gene is localized 100 to 200 kb centromeric of the NKG2 gene cluster and 300 to 400 kb telomeric of the STS marker D12S841. Genomic sequencing of the complete gene including promoter and intron sequences confirmed that the structure is similar to the mouse Ly49 genes. Screening of several cDNA libraries did not detect any transcripts of putative additional human LY49 genes. In addition, in the course of these studies several EST sequences were localized in the region, one immediately upstream of the LY49L gene. Genes and Immunity (2000) 1, 280-287.

Comparative Genomics of Natural Killer Cell Receptor Gene Clusters

“…Other NK surface molecules encoded in the human NKC include the activation-induced C-type lectin (AICL) [37], lectin-like transcript 1 (CLEC2D; also called OCIL and LLT1) [38], and CD69 [26]. Genes that encode products not found on NK cells, which are also located within the NKC, include alpha-2-macroglobulin (A2M) [26], oxidized low-density lipoprotein (lectin-like) receptor 1 (OLR1) [39], CLECSF12, CLEC1, and CLEC2 [40]. …”

A novel cluster of lectin-like receptor genes expressed in monocytic, dendritic and endothelial cells maps close to the NK receptor genes in the human NK gene complex

“…Beside proteins such as CD69 2, which are widely expressed in cells of the hematopoietic lineage, some are more restricted in cell type expression such as the lectin‐like NK cell receptors 3, 4. The lectin‐like NKR‐P1 and Ly49 genes, initially detected in rodent NK cells 5, and the CD94 and NKG2 genes, described first from human NK cells 6, 7, occur on syntenic regions of mouse chromosome 6 and human chromosome 12 8 – 10. These regions have therefore been termed NK gene complex (NKC).…”

Lectin-like oxidized LDL receptor-1 is a cell-adhesion molecule involved in endotoxin-induced inflammation

“…LOX-1 has an extracellular C-terminal lectin domain and belongs to the C-type lectin-like protein family with highest homology to natural killer (NK) cell receptors, which are involved in activation of NK cells when NK cells recognize tumor cells (1)(2)(3)(4). The genes of LOX-1 and NK cell receptors are colocalized in the short arm of chromosome 12, suggesting that these molecules have been evolved from a common precursor (5,6). Expression of LOX-1 is induced by inflammatory cytokines and oxidized LDL in vitro (7)(8)(9) and proatherogenic conditions in vivo, e.g., hypertension, hyperlipidemia, and diabetes mellitus (10)(11)(12)(13).…”