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

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.