Genomic organization of the human leukocyte immunoglobulin-like receptors within the leukocyte receptor complex on chromosome 19q13.4

Abstract

The leukocyte immunoglobulin (Ig)-like receptors (LIRs) comprise a family of cell surface receptors that couple to either activating or inhibitory signals depending on the nature of their transmembrane and cytoplasmic domains. We describe the organization and fine localization of the genes for LIR-1 and LIR-5, which are inhibitory receptors, and LIR-6, which is an activating receptor. The genomic organization of all three genes is highly conserved from the signal peptide through the membrane-proximal Ig domain but diverges thereafter depending on the inhibitory or activating nature of the gene product. The 3' untranslated region of the gene for LIR-6 contains a 37-base pair repeat not present in the LIR-1 or LIR-5 genes. 5' rapid amplification of cDNA ends defined the putative transcription initiation site of the LIR-5 gene, which is TATA-less. A nucleotide substitution in the LIR-5 gene led to loss of an intron present in the 5' untranslated region of the LIR-1 and LIR-6 genes. Differences in the genomic structure of these three LIR genes suggests possible mechanisms for their differential expression in cells of hematopoietic lineage. The three genes are in a region of Chromosome 19q13.4 that is immediately centromeric of the killer cell Ig-like receptor genes and are separated from one another by approximately 20 to 30 kb, suggesting that they arose by gene duplication from a common ancestor.