Natural killer cell receptors in the horse:: evidence for the existence of multiple transcribed LY49 genes

In rodents, the Ly49 family encodes natural killer (NK) receptors interacting with classical MHC class I molecules, whereas the corresponding receptors in primates are members of the killer cell immunoglobulin-like receptor (KIR) family. Recent evidence indicates that the cattle, domestic cat, dog, and pig have a single LY49 and multiple KIR genes, suggesting that predominant NK receptors in most non-rodent mammals might be KIR. Here, we show that the horse has at least six LY49 genes, five with an immunoreceptor tyrosine-based inhibition motif (ITIM) and one with arginine in the transmembrane region. Interestingly, none of the horse KIR-like cDNA clones isolated by library screening encoded molecules likely to function as NK receptors; four types of clones were KIR-Ig-like transcript (KIR-ILT) hybrids and contained premature stop codons and/or frameshift mutations, and two putative allelic sequences predicting KIR3DL molecules had mutated ITIM. To our knowledge, this is the first report suggesting that non-rodent mammals may use LY49 as NK receptors for classical MHC class I. We also show that horse spleen expresses ILT-like genes with unique domain organizations. Radiation hybrid mapping and fluorescence in situ hybridization localized horse LY49 and KIR/ILT genes to chromosomes 6q13 and 10p12, respectively.