Research article

Identification of the ancestral killer immunoglobulin-like receptor gene in primates

Jennifer G Sambrook^1* , Arman Bashirova^2,5* , Hanne Andersen^3,6 , Mike Piatak³ , George S Vernikos¹ , Penny Coggill¹ , Jeff D Lifson³ , Mary Carrington⁴ and Stephan Beck¹

¹  Immunogenomics Laboratory, Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 ISA, UK

²  Laboratory of Genomic Diversity, National Cancer Institute, SAIC-Frederick, MD 21702, USA

³  Retroviral Pathogenesis Laboratory, AIDS Vaccine Program, SAIC-Frederick, MD 21702, USA

⁴  Laboratory of Genomic Diversity, Basic Research Program, SAIC-Frederick, MD 21702, USA

⁵  current affiliation: Department of Infectious Diseases, School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA

⁶  current affiliation: BIOQUAL Inc, Rockville, MD 20850, USA

author email corresponding author email* Contributed equally

BMC Genomics 2006, 7:209doi:10.1186/1471-2164-7-209

Published:	15 August 2006

Abstract

Background

Killer Immunoglobulin-like Receptors (KIR) are essential immuno-surveillance molecules. They are expressed on natural killer and T cells, and interact with human leukocyte antigens. KIR genes are highly polymorphic and contribute vital variability to our immune system. Numerous KIR genes, belonging to five distinct lineages, have been identified in all primates examined thus far and shown to be rapidly evolving. Since few KIR remain orthologous between species, with only one of them, KIR2DL4, shown to be common to human, apes and monkeys, the evolution of the KIR gene family in primates remains unclear.

Results

Using comparative analyses, we have identified the ancestral KIR lineage (provisionally named KIR3DL0) in primates. We show KIR3DL0 to be highly conserved with the identification of orthologues in human (Homo sapiens), common chimpanzee (Pan troglodytes), gorilla (Gorilla gorilla), rhesus monkey (Macaca mulatta) and common marmoset (Callithrix jacchus). We predict KIR3DL0 to encode a functional molecule in all primates by demonstrating expression in human, chimpanzee and rhesus monkey. Using the rhesus monkey as a model, we further show the expression profile to be typical of KIR by quantitative measurement of KIR3DL0 from an enriched population of natural killer cells.

Conclusion

One reason why KIR3DL0 may have escaped discovery for so long is that, in human, it maps in between two related leukocyte immunoglobulin-like receptor clusters outside the known KIR gene cluster on Chromosome 19. Based on genomic, cDNA, expression and phylogenetic data, we report a novel lineage of immunoglobulin receptors belonging to the KIR family, which is highly conserved throughout 50 million years of primate evolution.