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 individuals 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 revealed two distinct lineages of ILT/LIR genes. These two lineages differ in both the nature and extent of their sequence polymorphism. The presence of certain transcription factor-related motifs in the 5' untranslated region of ILT/LIR cDNAs correlates with the specific cell types in which particular ILT/LIR genes are expressed. Although extensive gene duplications and conversion events have apparently forged the LRC, our results indicate striking conservation in the organization of the ILT/LIR genes when compared with the related and closely linked KIR genes. This suggests the evolutionary maintenance of a significant function consistent with the cellular distribution of the ILT/LIR proteins.
Young
N T
NT
Department of Structural Biology, Stranford University School of Medicine, CA 94305, USA. neil.young@nds.ox.ac.uk
Canavez
F
F
Uhrberg
M
M
Shum
B P
BP
Parham
P
P
D001483:Base Sequence; D017124:Conserved Sequence; D019143:Evolution, Molecular; D006239:Haplotypes; D006801:Humans; D007962:Leukocytes / Q000276:immunology*; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D011110:Polymorphism, Genetic; D011971:Receptors, Immunologic / Q000235:genetics*; D017422:Sequence Analysis, DNA
D011971:Receptors, Immunologic