Killer Cell Lectin-Like Receptors and the Natural Killer Cell Gene Complex

Abstract

The natural killer cell gene complex (NKC), which maps to the distal parts of mouse chromosome 6 and rat chromosome 4, and in the human to the short arm of chromosome 12, encodes type 2 membrane receptors belonging to the group V C-type lectin superfamily (CLSF), lacking the evolutionary conserved calcium/ saccharide binding amino acid residues found in other CLSF receptors. It contains all group V CLSF genes currently known, except Klrg1 which in rodents lies 6–7 Mb proximal to the NKC (see Fig. 1), and nothing but such genes, except Gabarapl1. Due to expansion of the Nkrp1 (Klrb) and in particular the Ly49 (Klra) multigene families the complex is particularly large in rodents, where it can be divided into three parts: a proximal part encoding Nkrp1 and Clr receptors, a middle part encoding a variety of group V CLSF receptors, and a large distal part encoding Ly49 receptors. In the rat the NKC spans 3.3 Mb and is predicted to contain 67 CLSF loci (including some pseudogenes), distributed as indicated in the figure. To the extent ligands are known, the NKC encoded receptors do not bind saccharides (with the exception of Dectin-11), but rather MHC class I and related ligands (rev. in2). Recently, mouse Nkrp1d and -f were shown to bind Clr molecules, providing the first example of CLSF receptor/ligand pairs3. Functionally the NKC encoded receptors have opposing regulatory roles on leukocyte activation, the activating mediating their effects via protein tyrosine kinases and the inhibitory via protein tyrosine phosphatases. Close to, but distinct from the NKC lies a smaller gene complex (called APLEC4) encoding opposing regulatory leukocyte receptors, but