A.

Gourraud, A. Meenagh, A. Cambon-Thomsen and D. Middleton, submitted). As expected, strong linkage disequilibrium between the KIR genes is driven by specific allelic associations in both regions. However, at the telomeric region KIR2DL4, KIR3DL1/S1 and KIR3DL2 have a particularly high number of alleles included in haplotypes in strong linkage disequilibrium, click here extending across relatively low linkage disequilibrium between pairwise loci. The data suggested that balancing between inhibitory and activating genes involves specific allele associations. Determination of alleles is also useful for positioning of KIR genes on a haplotype. Recently KIR2DS3*00103 RGFP966 has been shown to map to the centromeric side, and KIR2DS3*002 and KIR2DS3*003N to the telomeric sides of the haplotype.60KIR2DS5*002 was also shown to map to the same telomeric position as KIR2D3*002/003N, implying that these alleles belong to a single locus. We have extrapolated this work to our family data by determining the KIR2DS3 and KIR2DS5 alleles. KIR2DS3 was present on 67 (16%) of the 418 haplotypes. None of the four haplotypes positive for KIR2DS3*002 or KIR2DS3*003N had KIR2DS5, whereas in 53 haplotypes

positive for KIR2DS3*00103, KIR2DS5*002 was present in 17, KIR2DS5*002 being the only KIR2DS5 allele found in the Northern Ireland population.39 Ten haplotypes that had two copies of KIR2DS3 Neratinib concentration (*00103

and *002) were negative for KIR2DS5, It would therefore appear that KIR2DS3 alleles *002 and *003N are allelic to KIR2DS5*002 and KIR2DS3*00103 forms a separate gene, emphasizing that we have still much to learn of the generic make-up of KIR. A further level of diversity is provided by interaction of KIR and its HLA ligands and variation in expression of KIR genes on the NK cell. This topic and how NK cells are licensed by interaction with their HLA ligand has been covered in much greater depth in a recent review,61 but is worth mentioning briefly in the present context. Evidence of co-evolution is suggested by disease studies62,63 and population genetics.25,64 An inverse correlation exists in populations between the frequencies of the KIR A haplotype and the HLA-C2 group reducing the frequencies of potential pre-eclampsia pregnancies in which an increased prevalence of the AA genotype when the fetus carried the HLA-C2 group has been reported.65 Global studies on KIR3DL1/S1 diversity showed that positive selection was focused to the residues that interact with HLA and strong negative correlations between KIR3DS1 and its presumed HLA-Bw 4 ligand existed.25,64 In the latter study, the tendency was for inhibitory KIR to have positive correlations and activating KIR to have negative correlations, respectively, with their ligands.