Isotypic variation of novel immunoglobulin-like transcript/killer cell inhibitory receptor loci in the leukocyte receptor complex

Abstract

The leukocyte receptor complex (LRC) on human chromosome 19q13.4 encompasses at least four families of related genes: immunoglobulin-like transcripts (ILT), killer cell inhibitory receptors (KIR), the leukocyte-associated inhibitory receptors (LAIR) and the Fc § receptor (Fc § R). We determined the genomic organization of a region of DNA spanning the junction of the ILT and KIR gene complexes. Extensive sequence data were collected for ILT3, two novel genes, ILT9 and ILT10, and one novel KIR locus (KIRCI). These loci, along with other reported sequences from the region, encoded a leader sequence split into two exons, upstream of two to four immunoglobulin (Ig) domains, each on a separate exon. Downstream of the Ig domains, however, the organization differs markedly between inhibitory and activating ILT. These data are consistent with a highly conserved gene arrangement for all superfamily members suggesting duplication of primordial sequences. ILT3 and KIRCI were in the same head-to-tail orientation as has been described for other KIR loci which may facilitate addition or loss of genes between different haplotypes.

KIR2DL5, a Novel Killer-Cell Receptor with a D0-D2 Configuration of Ig-Like Domains

“…Only in the case of KIR2DL5 was an amplification product obtained, suggesting that the other three KIR genes are not expressed in PBMC. For KIR44, this apparent lack of expression agrees with the results obtained on KIRCI by Torkar et al (18).…”

“…Whereas KIR15 is likely a pseudogene of the type I KIR2D group, KIR44 and KIR48 show no structural anomalies in exons 2-5. Furthermore, the distinctive nonexpressed KIRCI gene (18), of which KIR44a and KIR44b seem to be allelic variants, has also been characterized from genomic DNA and shown to contain a complete putative open reading frame with no premature stop codons. Therefore, it remains uncertain whether KIR genes like KIR44/KIRCI and KIR48 are pseudogenes or if they can be expressed in certain circumstances, e.g., particular individuals, tissues, stages of development, or physiopathological situations.…”

“…These changes were confirmed in PCR products obtained from different experiments and most likely reflect allelic polymorphism. The two variants of KIR44, KIR44a, and KIR44b are closely related to the nonexpressed KIRCI sequence recently reported by Torkar et al (18), differing from it by 1 and 5 nucleotide substitutions, respectively. Thus KIR44a, KIR44b, and KIRCI probably constitute alleles of the same gene.…”

Cell Death Mechanisms Induced by Cytotoxic Lymphocytes

“…ILT6 is a receptor with scarce polymorphism (44) that activates T cell proliferation when produced by macrophages in a soluble form (45). Other receptors have also been identified, including ILT8, ILT9, and ILT10, but their functions are still unknown (46,47).…”

Paired Ig-like receptor homologs in birds and mammals share a common ancestor with mammalian Fc receptors

“…PIR-B has immunoreceptor tyrosine-based inhibitory motifs (ITIM) in its cytoplasmic region, which allows it to function as an inhibitory receptor (5)(6)(7)(8)(9)(10). Approximately eight Pira genes and a single Pirb gene reside in a centromeric region of mouse chromosome 7 that is syntenic with the leukocyte receptor complex (LRC) of genes located in the q13.4 region of human chromosome 19 (1,11,12).…”