Genomic organization and allelic polymorphism of the human killer cell inhibitory receptor gene KIR 103

Abstract

Killer cell inhibitory receptors (KIR) belong to the immunoglobulin super-family of molecules and are expressed on natural killer (NK) cells. The KIRs of the p58/p50 family have two immunoglobulin domains and are ligands for HLA-Cw antigens, whereas the p70/p70Δ family has three immunoglobulin domains and comprises ligands for HLA-B antigens and possibly some HLA-A antigens. Members of a third KIR family, KIR103, have two immunoglobulin domains but have highest nucleotide sequence homology to the p70 family. The ligands for KIR 103 on target cells are currently unknown. We here report the complete genomic organization of KIR103. It spans about 12 kb of DNA and consists of eight exons of which exon 1 and exon 2 encode the leader sequence. Exon 3 encodes the first immunoglobulin domain (γ1), and exon 4 encodes the main part of the second immunoglobulin domain (γ3), which also contains sequences contributed by exon 5 and exon 6. Exon 6 encodes the transmembrane domain, whereas exons 7 and 8 encode most of the cytoplasmic domain. KIR 103 is polymorphic, and two alleles, 103AS and 103LR, are defined in this study. Additional full-length cDNA clones for KIR 103 have been isolated and are shown to be formed by alternative mRNA splicing with exon skipping. Some of these truncated KIR 103 cDNA could encode shorter transmembrane molecules, whereas others lack the transmembrane domain and are candidate genes for secreted KIR products. KIR 103 is localized to the KIR genetic region on chromosome 19q13.4.