Discovery of two novel variants of KIR2DS5 reveals this gene to be a common component of human KIR ‘B’ haplotypes

Acknowledgments: This study was supported by grant AI17892 from the U.S. Public Health Service to P.P. C.V. was supported by a fellowship from the “Instituto de Salud Carlos III” , Spain (FIS BAE 98/5105); C.M.G. was supported by a grant from the Leukemia Research Foundation C.V.’s current address: Servicio de Inmunología, H.U. Clínica Puerta de Hierro, San Martín de Porres 4, 28035 Madrid, Spain. Abstract: The gene encoding the non‐inhibitory receptor KIR2DS5 has so far been represented by a single cDNA sequence, NKAT9. A previous study by polymerase chain reaction using sequence‐specific primers (PCR‐SSP) failed to detect NKAT9 in genomic DNA of 52 donors, which suggested that KIR2DS5 could be a rare gene. Here, we have characterized two novel variants of KIR2DS5 that differ from NKAT9 by 8 and 10 nucleotide substitutions. The frequency of KIR2DS5 was then re‐assessed by PCR‐SSP using primers specific for conserved sequences of all three known KIR2DS5 variants. We found KIR2DS5 is not a rare gene, but one present in 26% of 34 donors representing the major ethnic groups. Like other non‐inhibitory KIR, the distribution of KIR2DS5 is restricted to the ‘B’ subset of KIR‐gene haplotypes. Transcription of the KIR2DS5 gene was studied by reverse transcriptase (RT)‐PCR in natural killer (NK) cells from one donor and shown to follow the clonal distribution seen for most other KIR genes.