The genes and gene organization of the Ly49 region of the rat natural killer cell gene complex

Abstract

We here report the cDNA sequences of 11 new rat Ly49 genes with full and three with incomplete open reading frames. Although obtained from different inbred rat strains, these as well as six previously published cDNA represent non-allelic genes matching different loci in the Brown Norway (BN) rat genome, which is predicted to contain 34 Ly49 loci distributed over the distal part of the NK cell gene complex. Some of the cloned genes appear to be mutated to non-function in the BN genome, which harbors additional genes with full open reading frames, suggesting at least 26 non-allelic functional Ly49 genes in the rat. Of the encoded receptors, 13 are predicted to be inhibitory, eight to be activating, whereas five may be both ('bifunctional'). Phylogenetic analysis bears evidence of a highly dynamic genetic region, in which only the most distally localized Ly49 gene has a clear-cut mouse ortholog. In phylograms, the majority of the genes cluster into three subgroups with the genes mapping together, defining three chromosomal regions that seem to have undergone recent expansions. When comparing the lectin-like domains, the receptors form smaller subgroups, most containing at least one inhibitory and one activating or 'bifunctional' receptor, where close sequence similarities suggest recent homogenization events.

Complete elucidation of a minimal class I MHC natural killer cell receptor haplotype

“…In addition, a single rat Ly49 haplotype has also been sequenced and described. [34][35][36] The BN/SsNHsd/MCW inbred rat possesses 34 uninterrupted Ly49 genes with the same transcriptional orientation. In addition to a group of rat Ly49 that have no obvious orthologues in the mouse, one gene, rLy49i8, is a clear orthologue of mLy49b, and mLy49q is clearly more related to a large group of rat Ly49 than to the other mouse Ly49.…”

Distinctive Interactions at Multiple Site 2 Subsites by Allele-Specific Rat and Mouse Ly49 Determine Functional Binding and Class I MHC Specificity

“…Ly49 receptors belong to polygenic families comprised of numerous members both in the mouse and the rat (6,7). Inbred rat and mouse strains each have a characteristic Ly49 haplotype (8 -10), and allelic variation between Ly49 has been identified between mouse strains (11,12).…”

“…Inbred rat and mouse strains each have a characteristic Ly49 haplotype (8 -10), and allelic variation between Ly49 has been identified between mouse strains (11,12). Both activating and inhibitory Ly49 receptor types are found, with some activating/inhibitory hybrid receptors identified in the rat (7). Class I MHC (MHC I) 3 is the ligand for most well-studied activating and inhibitory murine Ly49 (4,13).…”

Ly49B Is Expressed on Multiple Subpopulations of Myeloid Cells

“…Ly49B cDNAs have been obtained from several tissue sources and predict a polypeptide that lacks a transmembrane charge and bears an ITIM in the cytoplasmic domain but which is significantly divergent from other Ly49s. Interestingly, Ly49B is the only member of the mouse Ly49 family that has an identifiable ortholog in the rat (8,9), suggesting it may have a distinctive and conserved function in murine species. We have now generated a series of mAbs that specifically recognize Ly49B and report here that Ly49B is not normally expressed on NK cells but instead is expressed on multiple subpopulations of myeloid cells that include granulocytes and macrophages.…”