Conserved organization of the ILT/LIR gene family within the polymorphic human leukocyte receptor complex

The human leukocyte receptor complex (LRC) at Chromosome 19q13.4 encodes Ig superfamily proteins which regulate the function of various hematopoietic cell types. We investigated characteristics of the Ig-like transcript (ILT) /leukocyte Ig-like receptor (LIR) group of LRC genes in comparison with the other major LRC loci encoding the killer cell Ig-like receptors (KIRs). In direct contrast to KIR genes, the ILT/LIR loci of ethnically diverse indiv iduals did not display haplotypic variations in gene number. Investigation of gene expression identified novel cDNA sequences related to the ILT2/LIR1 , ILT4/LIR2., ILT3/LIR5. and ILT7 loci. while phylogenetic analysis reveale d two distinct lineages of ILT/ LIR genes. These two lineages differ in bot h the nature and extent of their sequence polymorphism. The presence of cer tain transcription factor-related motifs in the 5 ' untranslated region of ILT/LIR cDNAs correlates with the specific cell types in which particular I LT/LIR genes are expressed. Although extensive gene duplications and conver sion events have apparently forged the LRC, our results indicate striking c onservation in the organization of the ILT/ LIR genes when compared with th e related and closely linked KIR genes. This suggests the evolutionary main tenance of a significant function consistent with the cellular distribution of the ILT/LIR proteins.